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COPYRIGHT DEPOSIT. 



TEXT BOOK 



OF 



COMPARATIVE 

GENERAL PATHOLOGY 



FOR 



Practitioners and Students of Veterinary Medicine 

BY 

PROFESSOR DR. TH. K1TT 

OF MUNICH 



Authorized Translation 

BY 

DR. WILLIAM W. CADBURY 

Assistant Demonstrator of Pathology in the University of Pennsylvania 



Edited with Notes and Additional Illustrations 

BY 

DR. ALLEN J. SMITH 

Professor of Pathology in the University of Pennsylvania 



Illustrated with Four Colored Plates and One Hundred and 
Thirty-one Text Illustrations 



CHICAGO 

W. T. KEENER & CO 

1 906 



^ 



<&\ 



UMAKY if CONGRESS 

Twe Ceptef Received 

OCT 31 1906 

A CepyrffM Entry 

<*.'>, jtrt> 

CUSS K XXCmNo, 



Copyrighted, 1906 
Bv W. T. Keener 



PREFACE TO GERMAN EDITION 

The introduction of students of veterinary medicine to the 
study of pathology, because of the lack up to the present time of 
a German text book of general pathology adapted to diseases 
of animals, has depended chiefly upon works written for the 
practitioner of human medicine; the lectures of instructors in vet- 
erinary medicine and students' notes, made with more or less 
accuracy, supplying the necessary additions and explanations. 

Only one work, the Text Book of General Pathological Anat- 
omy by Birch-Hirschfeld, has been amended from the standpoint 
of our special branch of medicine, by the addition of veterinary- 
medical paragraphs from the facile pen of Johne, so as to seem 
adapted for students in veterinary schools ; but it is confined to 
pathological anatomy, and the physiological and serological fea- 
tures, the manifestation of functional impairments, pathogenesis, 
etc., require further reference to special works. 

As an introduction and foundation for appreciation of the 
practice of veterinary medicine, to be studied and put into applica- 
tion in the latter portions of the college curriculum, after com- 
pletion of the courses in anatomy, physiology and the natural 
sciences, the student should be given a general idea of the mean- 
ing of disease, the aetiology of diseases, of the make-up of our 
medical knowledge and of the principles of classification, as well 
as a general familiarity with the alterations in structure and func- 
tion met in disease. It is for this reason that lectures on general 
pathology are provided, introductory to the special applied 
branches of study.. The need of a work concisely comprehending 
such features has determined me to undertake the task of pre- 
paring a condensed outline of the fundamental facts of pathology 
with special adaptations to the requirements of veterinarians. Of 
course, it has been necessary to make use of much material from 
works intended for the student of human medicine, and T am 
vividlv reminded of the old sentence in the Latin errammar — "Plinius 



iv Preface to German Edition. 

nullum librum legit, ex quo nan excerpserit." I therefore ac- 
knowledge at the outset and at various places in the text, that I 
have freely employed in the preparation of the following text- 
book the works of Ribbert, Perls, Krehl, Durk, Samuel, Thoma, 
Birsch-Hirschfeld, Johne, Uhle and Wagner, as it is in fact prac- 
tically impossible to write an authoritative work on general 
pathology without dependence upon other authors. 

The scientific development of veterinary medicine depends 
primarily upon the same principles which obtain in human med- 
icine. The propositions and methods of research which were 
originally employed in the study of human pathology, are for us, 
too, fundamentals for the appreciation and investigation of the 
nature of the animal diseases. Every new advance in human 
medicine in the fields of anatomy, physiology, the use of the micro- 
scope, technique of clinical study, surgical and therapeutic meth- 
ods, bacteriological and practical hygiene, has been of advantage 
to comparative medicine, and, mutatis mutandis, has found an 
application in veterinary practice, and has pointed out the way 
for advanced work in our own branch. There has been much as- 
sistance afforded, too, in the fact that many of the discoveries 
oi value to human medicine have been made from experimental 
studies upon animals, and the principles of general pathology par- 
ticularly have been fundamentally proven by comparative study 
of the anatomy and physiology of animals; both branches of med- 
icine, therefore, drawing from the same sources and having a 
common field of work. 

Apart from these considerations, however, the representatives 
of veterinary medicine have, by their independent achievements, 
built up the pillars and walls of their own scientific temple, with 
such multiplicity of specialized purposes and requirements that 
the method and practice of veterinary medical instruction have 
come to have a peculiar character of their own. Consideration 
of these requirements is attempted in this volume. 

It is well known to every teacher who is required to act as 
an examiner, how difficult it often is for the candidates in an 
examination to express what they well know and how, no matter 
how clearly the questions may be presented, or what statements 
are made suggesting a proper answer, this or that really capable 
student finds himself forced to struggle with words and is handi- 
capped in expressing his ideas. In order to lessen these diffi- 
culties for students, I have endeavored to frame my definitions 



Preface to German Edition. v 

concisely, to present the positive facts in as clear and as brief 
a manner as possible, and to limit to what is absolutely essential 
the incomplete, uncertain and controversial points of "study, the 
elaborate discussion of which is usually confusing and tends to 
weary the student. Of course, important objections and ques- 
tioned points in theories have been noticed, lest the student be 
led to mere memorization and superficial study, and in order that he 
may be stimulated to think. I believe that the work will be found 
useful to the practising veterinarian as well, as a general presenta- 
tion of the most recent position of the science. 

I have omitted description of the individual types of animal 
parasites and bacteria and taken up only in this connection their 
bearings upon general pathology. The scope of the work would 
otherwise have been too large; and full details upon these sub- 
jects may be found in the part devoted to special pathology 
(Lehrbuch der pathol. Anatomie der Haustiere. II. Aufl. 1901. 
F. Enke, Stuttgart) and in my Lehrbuch der Bakterienkunde und 
pathol. Mikroskopie (IV. Aufl. M. Perles, Wien, 1903). The 
subject of malformations is also treated of at the beginning of the 
special section just mentioned, and a repetition is therefore super- 
fluous. 

The publisher has presented the volume in an excellence of 
style which places me under special obligation to him. 

Numerous new illustrations are included, prepared by the ar- 
tistic hand of K. Dirr; some of the cuts I have borrowed from 
the works of authors cited in the text. For a number of photo- 
graphs I must thank for their kindness the veterinary physicians 
Dr. Jakob and Dr. W. Ernst, the latter of whom, a skillful micro- 
scopist and bacteriologist, has been engaged for a number of 
years in my institution and has aided me in a most valuable man- 
ner in carrying on investigations bearing upon my studies. 

Munich. TH. KITT. 



PREFACE TO AMERICAN EDITION 

The work of translating and preparing for publication the 
following edition of Kitt's General Pathology has been a pleasure, 
because of the real value of the work and because both editor and 
translator have believed the labor a service to the profession. As 
Professor Kitt states in the preface to the German edition, it is 
practically the only work devoted to a discussion of general 
pathology from the standpoint of the veterinarian ; and the need 
of such a work has long been manifest to every teacher of pathol- 
ogy in charge of students of veterinary medicine. The impres- 
sions given by any book upon pathology, even the best, which has 
been framed primarily for use in connection with human medicine, 
are often unfortunate from the inaptness of the descriptions of 
lesions for the needs of men studying comparative medicine. It is 
undoubtedly true that the general processes of disease are funda- 
mentally the same in whatever subject they occur; but the 
varieties of appearances of one and the same type of lesion in 
different species may well be sufficiently marked to make the 
descriptions based upon the changes met in any given animal 
confusing and perhaps inadequate for students, whose experience 
in the earlier years is anything but extensive. The differences, 
for example, in the appearances of a tuberculous caseated area in 
man, in the cow, hog, horse, or in carnivora, well illustrate the 
point in mind ; or the differences in bulk and in other character- 
istics of various tumors as met in man and in the large domestic 
animals serve as an example. The adaptation of the present 
volume to the needs of students who, as Professor Kitt points 
out, have had to accept, as a rule, the descriptions of lesions as 
seen in man and then amend them by notes from lectures, has 
strongly appealed to us as instructors of veterinary students, and 
will find, we believe, an equal appreciation from others whose 
work has fallen in similar lines. 

The book reflects well the tendency of modern pathological 



viii Preface to American Edition. 

teaching to devote considerable effort to direct the thought of the 
reader along lines of pathological physiology, to make the student 
reason for himself from given anatomical data and appearances 
as to the necessary functional faults and failures which would 
follow. Pathological anatomy is, of course, fundamental and 
finds its place on every page ; but the author has had in mind 
the application of pathology to the living diseased animal, and 
the anatomical descriptions and discussions serve as a basis for 
explanation of the development of the processes and the func- 
tional faults the diseased animal must necessarily manifest. The 
chapters on disturbances of the circulatory, respiratory and other 
functions are, of course, brief, but they are by no means super- 
ficial and indicate well the lines of necessary study for the prac- 
ticing physician and are stimulative to thought on the part of 
the student. 

The value of such a work is not confined to the veterinarian ; 
the intimate relations comparative pathology bears to the study of 
human medicine and the need that experimentalists should be in 
the best possible position to appreciate the reactions peculiar to 
various species of experiment animals require of pathologists 
broader and broader powers of recognition. Much of the criticism 
against animal experimentation has its only force in that in the 
hands of men unfamiliar with the animals utilized, both in their 
normal life and in their pathological reactions, the best results 
are not obtained, at least not appreciated, by such workers in 
return for the sacrifice entailed. The best is accomplished, other 
things being equal, by men whose training comprehends a broad 
biological and physiological experience and who are familiar with 
the peculiarities of physiological reaction and anatomical changes 
to be met in the animals employed under the operation of given 
pathogenic influences. Such works as the present volume, intro- 
ductory to the fuller Special Pathology in the companion volumes 
of the German edition, have therefore a proper place on the 
shelves of every pathologist, whether his work deals with human 
or with comparative problems as its major field. 

In presenting the book to our English-speaking colleagues and 
students, the editor and translator have endeavored to follow 
closely Professor Kitt's language, although no attempt to be abso- 
lutely literal in the translation has been made. Doubtless the 
effort to translate the German idiom to its English equivalent has 
often failed ; and we both appreciate the fact that unwittingly the 



Preface to American Edition. ix 

verbiage of the translation has sometimes, in the endeavor to keep 
close to the original, come to be somewhat complicated for English 
text. The editorial notes, which are always enclosed in special 
brackets ([ ]), have purposely been kept within brief limits, 
because of our realization of the sufficiency of the work for the 
introductory purposes for which it is intended by the author, and 
because of a desire to keep the size of the book near the limits 
of the original edition. We feel that for use at the hands of 
graduate physicians the book as it stands meets the purpose for 
which it was written ; for student purposes, as a handbook as 
well as a general text, it would perhaps have been regarded as 
an advantage to have added descriptive matter to the tables of 
the vegetable and animal parasitic organisms and to have ex- 
panded the text somewhat in connection with minute anatomy, 
thus giving it a fuller adaptation to laboratory studies. A num- 
ber of illustrations have been generously added by the publishers 
with this latter view in mind. These illustrations, made by the 
well-known artist, Louis Schmidt, include figures 63, 82, 86, 89, 
91, 97, 101, 102, 103, 104, in and 125; and it is thought that 
the book, with such additions, will find a fuller place as an aid to 
the student in the laboratory of pathological histology. 

The publishers have not spared expense to make this work 
possible in the translated form, and by their interest have, we 
feel, placed the profession under obligations. For ourselves the 
venture is in no sense a financial one, and if others will find, as 
we hope, that our efforts have aided in pressing forward the 
general good for both veterinary and human medicine, our com- 
pensation will be ample. 

Allen J. Smith. 
William W. Cadbury. 

September, 1906. • 



TABLE OF CONTENTS 



PAGE 

Preface to German Edition iii 

Preface to American Edition vii 

Introduction i 

Definition of Pathology ; Conceptions of Disease ; Pro- 
cesses of Disease. 

History of Pathology 10 

Disposition Toward Disease 16 

Predisposition and Immunity ; Defensive Mechanisms 
of the Body. 

Congenital and Inherited Disease 30 

Placental, Intrauterine Origin of Disease ; Germinal 
Variation ; Germinative Predisposition ; Hereditary 
Conditions. 

Causes of Disease 35 

Disturbances of Nutrition and Alimentation 36 

Respiratory Disturbances 38 

Excessive Functional Activity. 40 

Thermic Influences 41 

Chilling 45 

Electrical Agencies 48 

Mechanical and Traumatic Agencies 49 

Chemical or Toxic Agents 50 

Microbic or Infectious Agents 54 

Animal Parasites 76 

Course and Termination of Disease 91 

Symptoms, Diagnosis, Natural and Artificial Means of 
Recovery, Death. 

Circulatory Disturbances [06 

I Hsturbances of Cardiac Efficiency 106 

Local Variations in Amount of I Mood in a part (Hy- 
peremia, Anaemia) 109 



xii Table of Contents. 

* 

' PAGE 

Haemorrhage 119 

Dropsy and (Edema 

Occlusion of Blood Vessels (Thrombosis and Embo- 
lism) - 

Alterations of the Blood (Plethora, the Anaemias, 
Leukaemia) 156 

Disturbances of Metabolism, Retrograde Changes and Necrotic 

Processes . 165 

Disturbances of Heat Regulation, Overheating, Fever. 165 

Necrosis 176 

Atrophy 185 

Cloudy Swelling 190 

The Fatty Changes 192 

Hyaline Degeneration 199 

Mucoid Degeneration 202 

Colloid Degeneration 204 

Glycogenic Infiltration 205 

Amyloid Degeneration 205 

Pigmentation 209 

Calcification and Concrement Formation. . . . • 216 

Processes of Repair and New Formation . 232 

Regeneration 232 

Transplantation 251 

Hypertrophy 254 

Inflammation 258 

Tuberculosis 291 

Glanders 311 

Actinomycosis 318 

Botryomycosis *. 324 

Tumors ( Autoblastomata) 325 

Fibroma (p. 341) — -Lipoma (p. 346) — Myxoma (p. 
349) — Chondroma (p. 350) — Osteoma (p. 353) — 
Myoma (p. 356) — Neuroma, Glioma (p. 358) — Hem- 
angioma, Lymphangioma (p. 362) — Sarcoma (p. 365) 
— Lymphoma (p. 372) — Melanoma (p. 377) — Endo-, 
Peri-thelioma, Cholcsteoma (p. 380) — Papilloma (p. 
383) — Adenoma (p. 388) — Cancers (p. 394) — Epithe- 
lial Cysts, Dermoid Cysts (p. 415) — Adenocystoma (p. 
418) — Odontoma (p. 419) — Teratoma, Embryoma (p. 
421). 



* Table of Contents. xiii 

PAGE 

Functional Disturbances 423 

Nervous Disturbances; Disturbances of Motion 423 

Digestive Disturbances 436 

Respiratory Disturbances 448 

Disturbances of Urinary Excretion 454 

Disturbances of the Thyroid Function 459 

Disturbances of the Sexual Function 461 

. Disturbances of the Cutaneous Function 462 

Index 465 



INTRODUCTION 

Pathology (to irddos, suffering; 6 \6yos, science) may be defined 
as the natural history of diseases, or as the scientific study 
of diseases. The terms "disease," "disordered" and "morbid" are 
employed to indicate the existence of disturbances of the physio- 
logical activity of the organs ; that is, the presence of some devia- 
tion from the anatomical and chemical relations of the body- 
constituents which exceeds the limits of physiological variation and 
which calls forth such disturbances. 

In ordinary life we designate as "health" a state of the body in 
which the vital manifestations (nutrition, metabolism, motility, sen- 
sation, psychical activity) are carried on in harmony; and it is as- 
sumed in addition that the various organs are of normal structure, 
and that the individual experiences a feeling of well-being. On 
the other hand the term "disease" carries with it a conception 
opposed to this so-called health, that of an irregularity of function 
and of impairment of efficiency of the organs and systems of 
organs, accompanied as a rule by a feeling of discomfort.- 

The distinctions between these two conceptions merge, however, 
and are lost when we consider the infinite gradations between health 
and disease, and as we are required to employ the terms, either 
empirically or scientifically, in a narrower or broader sense. There 
might exist, for example, an organ of distinctly faulty structure in 
an individual without causing any appreciable disturbance of the 
general health, as a malformed kidney, or a curvature of the spine. 
One of two paired organs, as a lobe of the thyroid or one of the 
kidneys, may be anatomically so altered and incapable of function 
as to merit being considered diseased ; nevertheless the individual 
may feel well and live many years. Moreover in healthy bodies 
there may now and again be evinced deviations from the normal 
vital manifestations which may simulate morbid disturbances, but 
which are not felt or regarded as such because of their brief dura- 
tion, because they are soon corrected 1>\ the protective and regu- 
lating mechanism of the body, or are a< most expressions of such 



2 Introduction. 

adjustments ; for example, after marching there may be a brief 
elevation of body temperature even to fever heat. In considering a 
body corpulent from fat deposit, one may be at a loss to indicate 
whether the corpulence is but a normal condition, or whether a 
really morbid state of obesity has commenced ; and, at least in the 
popular mind, intoxication from alcohol is certainly not to be con- 
sidered as a disease although in the stricter interpretation we are 
forced to look upon it as a departure from the state of health. 

Besides the term Disease, therefore, general convenience of 
speech requires the use of such terms as Sickness, Indisposition, 
Feeble Health, Defect, Fault or Damage, and limits the employ- 
ment of "disease" to such conditions in which the structural and 
functional disturbances go so far as to hinder the more important 
vital processes, to cause pain and to impair in an essential manner 
the vital phenomena of the organism as a whole. By the expressions 
"feeble health," "debility" (imbecillitas) is to be understood a 
diminished power of bodily resistance to pathogenic influences ; 
"sickness" or "indisposition" is used when there is a subjective 
feeling of impaired health and where but minor grades of disease 
actually exist. "Defects," "damages" and "faults" are conditions in 
which certain parts of the body appear structurally abnormal and 
do not properly functionate ; conditions in which the derangements 
have come to a definite standstill, and only under special conditions 
are likely to give rise to further morbid manifestations. Should 
these be congenital, arising in the period of foetal life, they are 
spoken of as Malformations, Congenital Defects, Developmental 
Faults, Vitia Congenita; if acquired after birth as sequels of dis- 
ease (wholly or partly removed), or if the results of mechanical in- 
fluences, as Acquired Deformities, Mutilations, or Vitia Acquisita. 

In its proper meaning the term Disease has no reference to any 
entity or thing, but to more or less complicated processes and con- 
ditions which are evidences of disturbances of the physiological 
constitution and activity of the body ; this applying to the individual 
cells as well as to the whole group of cells making up the organism. 
Diseases are therefore to be distinguished as diseases of the cells 
or structural elements of the organs, as diseases of the tissues, 
of organs, of systems, and of the individual or organism as a whole. 
[Inasmuch as life is but an expression of a harmony of structural 
and functional relation between the cellular constituents of the body 
among themselves and of the maintenance of efficient adaptability to 
the bodily environment, disease should be thought of as being made 



Nature of Disease. . 3 

up of any change of structure or modification of function which 
may impair this harmony and adaptability to cellular or bodily 
surroundings. And individual diseases may then be ^understood as 
including special groups of such modifications of structure and 
function, these groups varying in the isolated affections in type, 
distribution and number.] The processes which go to make 
up a disease are not fundamentally different from the physiological 
processes, are not features foreign to the operation and structure 
of the healthy body, but are to be directly referred to these ; the only 
difference being that in disease they manifest themselves in a site, 
at a time or in a degree other than in the normal state of the body. 
Pathological processes may therefore, as by Virchow, be con- 
sidered as heterotopic, hetero chronic and heterometric physiologi- 
cal processes (trepos, another; 6 towos, place; xp° v os, time; iitrpov, 
amount). As an illustration: a haemorrhage into the ovary, caused 
by the bursting of a follicle and ovulation, is normal, but a 
haemorrhage into the brain is abnormal ; unconsciousness in sleep 
is normal, but at an unusual time and in pronounced degree, as in 
swooning, is pathological. Almost invariably physiological ana- 
logies are to be found, in comparison with which the alterations of 
disease are manifestly but quantitative variations or variations of 
place and time. The gastric mucous membrane, when the stomach 
is full and engorged during the process of digestion, is very full of 
blood and red; in another part of the body, as the conjunctival 
mucous membrane, this same redness and congestion would be 
pathological. The endometrium normally sheds epithelial cells and 
leucocytes in the lochial secretion in considerable numbers after the 
removal of the placenta ; were this not merely temporary but of per- 
manent duration the condition would constitute a pathological one, 
a catarrh. In the tumors or pathological new growths, which are 
apparently so foreign to the general organism, there are to be found 
only the same tissue elements as belong to the normal body, which 
however possess a power of growth which is abnormal. Even the 
phenomena of death have their physiological counterpart, as in the 
mummification of the umbilical cord. * 

The various pathological processes may be classed as follows : 
(1) Anatomical-pathological processes (gross pathological-ana- 
tomical or pathological-histological) : Here are included all 
changes of structure or lesions whether of the gross organs or 
of the tissues and cells, as lesions of continuity of the skin and 
musculature (wounds), changes in consistence (as cerebral soften- 



4 Introduction. 

ing or induration of the liver), occupation of spaces and formation 
of false membranes by fibrinous material (pleurisy, croup), micro- 
scopic changes in the cells (karyolysis, fatty infiltration). 
(2) Chemico-'pathological processes: Quantitative and qualitative 
changes of the chemical constituents of the animal organism and its 
parts (metabolic faults), as the presence of bile in the blood, albu- 
men in the urine, uric acid in the joints or abnormal proportion of 
water in the blood. [Here might well be included, too, the ex- 
cessive formation or uric acid or its salts, of the faulty carbohy- 
drate changes of diabetes, the development of faulty types of 
albumen in the blood and within the cells, the toxic changes of 
uraemia and other intoxications, those essentially chemical processes 
which underlie in an important degree the changes produced by 
infections, as well as a wide group of more or less indefinite meta- 
bolic diseases.] 

(3) Functional-pathological or symptomatic disturbances (some- 
times spoken of as dynamic disturbances) : These are faults in the 
nicety of balance of the various physiological activities of the or- 
ganism, as the occurrence of convulsions, pain, unconsciousness, 
labored breathing, diarrhoea or dribbling urine. Functional dis- 
turbances are usually caused by structural and metabolic faults. 
Commonly the latter are primary, as in physiological life the effi- 
ciency, growth and development of the organs are dependent upon 
the chemical processes of nutrition and metabolism. Our knowl- 
edge of the morphological and chemical basis of functional de- 
rangements is, however, 'incomplete. 

Consideration, description and investigation of pathological 
variations may therefore be divided into (a) Pathological Morphology 
or Anatomy, (b) Pathological Chemistry and (c) Symptomatology, 
together with (d) considerations of the influences under which dis- 
eases develop, and the actual causes of disease (Aetiology: atria, 
cause). In the origin of disease some cause is apt to act so as to 
bring about material changes, chemical and physical, pathological 
lesions (Iced ere, to injure) of the component elements and organs, 
as well, as the counteraction or pathological reaction on the part 
of these same elements and organs, both of which manifest them- 
selves by functional disturbances (symptoms or signs of disease). 

That phase of pathology which seeks to explain the development 
of lesions and symptoms constitutes Pathogenesis ( ■$ y<W«, de- 
velopment, beginning) ; that which concerns the observation of 
the chronological succession of disease-events, the onset, course 



Divisions of Pathology. 5 

and termination of disease, is known as Nosology (77 v6aos, sick- 
ness). 

The object of pathology is primarily the acquisition of knowl- 
edge of the laws which govern pathological changes {P atho gnomy , 
from yiypibo-Kw, to become acquainted with) ; in addition, to point 
how and why certain lesions and reactions must follow certain 
causes. Dealing in its broadest sense with life under abnormal con- 
ditions, pathology presents itself as Pathological Physiology; and 
moreover provides a scientific basis for the prevention and cure of 
disease, and thus the foundation of rational Prophylaxis (-rrpo- 
(pv\&<r<ru, to prevent or guard against something) and Therapy 
i] depairda, therapeutics, from depairevw , to attend, to heal). 

For convenience in instruction pathology is separated into two 
divisions : General Pathology and Special Pathology. This is done 
with the purpose of facilitating a systematic presentation of the 
wide scope of the study; general pathology dealing with the ele- 
mentary pathological processes and their causes without reference 
to their site in the body, and being thus introductory to special 
pathology, in which the various individual phenomena of morbid 
change in the different organs and systems find expression. 

With the healthy living individual as its starting point, and basing 
its comparisons upon the average normal structure and ordinary 
physiological functions of the organism, pathology is dependent 
upon anatomy, physiology, chemistry and physics as its guides. A 
clear understanding or comprehension of its processes is impossible 
without a thorough knowledge of the organization of the animal 
body; a knowledge which includes the external configuration, the 
internal structure, the vital phenomena of health and the functions 
of each of the different organs. Chemistry and physics are essential 
for such a comprehension, both in their own immediate relations 
and, too, in connection with zoology and botany bearing upon the 
interpretation of disease causes. It is possible that one without 
this knowledge, a layman, may recognize various common morbid 
conditions (as wounds, fractures of bones, catarrhs, blisters, etc.), 
may name them correctly, and even treat them correctly on the basis 
of traditional information empirically acquired ; and by frequent ob- 
servance of such conditions may accumulate a fair amount of skill 
in their diagnosis and treatment. This is known as empirical knowl- 
edge. But to be able to scientifically interpret the complex picture 
presented by disease, to understand the whole trend of the process, 
its signs, its inception, and its recovery, and moreover to practice a 



6 Introduction. 

rational method of treatment, is possible only to those who have 
become versed in these basic branches of learning. Only unpre- 
judiced observation of nature and careful scientific study based 
upon anatomy and physiology, can give such insight. 'To attempt 
to guess by speculation what is hard to learn even by thorough 
investigation has failed in this as in every other field of natural 
philosophy/' (Samuel.) 'The enigmas of disease are far too 
complex, the intermingling of forces in the higher forms of life 
are far too involved, that thought alone should successfully recog- 
nize such threads, not even to mention their absolute demonstra- 
tion. The pages of general pathology are filled with the vanity of 
such attempts." (Samuel.) 

Our knowledge of disease is primarily obtained from observa- 
tion of the external appearances of diseased human beings and ani- 
mals, from accumulation of experience with the external manifesta- 
tions of disease {clinical observation). As long as autopsies were 
not permitted upon the bodies of the dead, diseases received con- 
sideration only from such external features ; and there existed only 
a symptomatic classification of disease. It was customary to speak 
of jaundice, dropsy, ardent fevers, nervous fever, etc., as diseases, 
and to endeavor to explain by clever theories and all sorts of base- 
less ideas the origin of internal affections, whose cause and location 
were for the most part unknown. They were regarded as mysteri- 
ous occurrences, for which evil spirits or the influence of the stars 
on the lower world should be held responsible; and knowledge of 
pathology and the art of healing as well had to be groped for in 
darkness. Nothing beyond those morbid conditions caused by 
wounds, by gross external violence, or such affections of the skin or 
mucous surfaces which were patent to the eye, was dealt with in a 
less confused manner. 

In many lines the physicians of antiquity, who sought to deter- 
mine the nature of disease by dissection of human and animal 
cadavers, gained astonishing experience, practical skill and an ac- 
quaintance with the subjects, as is manifest from the clever experi- 
ments and methodical investigations of these early thinkers. But 
in the centuries of the Middle Ages, so barren of medical advance- 
ment, even long after the founding of the universities (which oc- 
casionally did succeed in making isolated discoveries of value in 
connection with physiology) medical science became stationary and 
fixed, hemmed in between philosophical systems on the one hand 
and all manner of outgrowths from a purely speculative and 



Sources of Pathology. J 

hypothesis-building science on the other. The learned doctors, with 
their schools of practically nothing more than mere dogma, who 
had no acquaintance with the structure and vital functions of the 
body save what could be gained from its exterior, knew little more 
than the charlatans of their times. Veterinary medicine was prac- 
ticed by butchers, farriers and grooms, whose information and 
practical knowledge were based upon the doctrines, conceptions 
and recipes handed down from former generations. 

At the present time clinical observation is no longer limited to 
the mere detection of the external signs of disease, but seeks an 
explanation for them, searches for evidence of the internal morbid 
processes and for the precise location and for the causes of disease, 
calling to its aid every means of anatomical and physiological in- 
vestigation and contributing materially to the complete develop- 
mental history of disease. 

In point of time the real development of pathological science 
corresponds with the period when first the study of the exact loca- 
tion of disease was begun with the aid of the dissecting scalpel and 
the microscope. Morbid anatomy came to be recognized as the 
foundation stone of scientific medicine, and remains the most im- 
portant landmark in experimental studies. It was recognized that 
definite symptoms are related with certain structural alterations, 
that it is possible to make inferences as to the altered state and 
structure of the organs from given disturbances of function, and 
that the symptomatology of a case may thus furnish a basis for 
the anatomical diagnosis and the anatomical conception of the dis- 
ease in hand. Many of the alterations of disease are of such a 
character that the position, shape, consistence, color, weight and 
contents of the parts affected are strikingly different from the 
characteristics in health, and even the unaided eye sees at once 
why symptoms must have been induced ; and from the study of 
such evidence afforded by the dead bodies of diseased human beings 
and animals there has been accumulated a large amount of data ana 
statistics toward the establishment of a clear insight into the develop- 
ment, cause and termination of disease. Visceral anatomy along 
with visceral physiology has taught us what we know of the prin- 
ciples governing the action of the heart, the circulation of the blood, 
atmospheric interchange in the lungs, the functions of the digestive 
and urogenital tracts, and no little part of the pathology of the 
sensory organs ; and it is quite possible for one to draw conclusions 
from given anatomical changes how the mechanism of the grosser 



8 Introduction. 

parts of the body is interfered with, fails or becomes irregular, 
as in case of cardiac obstruction, obstruction of the blood vessels 
or intestinal canal by clots of blood or foreign bodies, or how in- 
testinal displacement or unusual taxing of the organs must or 
may lead to disturbances. The entire group of physiological 
methods of investigation are of value in the solution of pathological 
problems ; physics and chemistry aid in explanation and find the 
most varied application in their study. There has been developed 
in pathologv along the lines of its special studies a series of prac- 
tical methods of animal experimentation, known as Experimental 
Pathology, affording accurate information in many of the problems 
of pathogenesis and supplying valuable demonstrations of the cor- 
rectness of our best established observations and conclusions. One 
may at will, by operative procedure upon living animals, by ligation 
or occlusion of blood vessels or ducts of glands, produce and imitate 
mechanical changes of various types ; and it is quite possible by 
killing the experiment animal at any time to note precisely the 
anatomical changes and progress of the disease thus induced, from 
which the course of actual diseases of a corresponding type have 
come to be well appreciated. By operative removal of some organ 
or part of an organ, it is possible to obtain an idea as to the results 
which are likely to follow analogous disease processes in the same 
part, as in case of the thyroid gland, liver, kidney or adrenal. All 
bur knowledge of regenerative growth of tissues, the healing of 
wounds, the union of fractured bones and of the general process of 
inflammation we owe directly to experimental studies on animals. 
By administering to animals various types of material of ap- 
parently poisonous character, it has been possible to study the action 
of a wide range of substances and to acquire the essential basis 
for diagnosis of the intoxications. The complete life history of the 
animal parasites, their development and multiplication in the human 
and animal body, and the diseases caused by them, have been worked 
out by means of animal experimentation in a really classical man- 
ner ; and the practical application of this knowledge in food exami- 
nation, in meat inspection and in other lines of prophylaxis against 
disease, are exceedingly numerous and have led to marked diminu- 
tion of such diseases as hydatids, trichinosis and mange. But above 
all else animal experimentation has lifted the dark cloud which 
formerly obscured the nature of infectious diseases; and only from 
successful attempts in transmission by inoculation has it been pos- 
sible to explain and obtain precise knowledge as to the real nature 



Importance of Pathology. 9 

of plagues and their development. As long as these methods were 
not employed superstition and fear dominated mankind whenever a 
pestilence appeared. To-day, with realization of the conditions 
essential for infection and the modes of transmission, medical 
acumen has determined the surest preventive measures for con- 
trolling and combatting these diseases ; and even the worst epi- 
demics, as of plague and cholera, have largely lost their terrors. 
With confidence the work of extirpation is being carried forward, 
and medical science, crowned with success, has completely stamped 
out a number of these infections and is daily solving the difficulties 
in the prevention and cure of such evils. 

To sympathetic persons it may indeed seem a serious thing that 
we be forced for our own advantage to make use of the sufferings 
of lower animals in order to avert such dangers from ourselves 
and to purchase by animal sacrifice the means of combatting con- 
tagion. But the instinct of self-preservation impels man, just as 
the necessity for food with any animal demands the death of other 
creatures. The slaughter of animals for sport is far worse, and 
productive of more pain to them ; and many of the methods of kill- 
ing in the kitchen of the epicure are much less excusable than, any 
of the practices in the whole range of deplored animal inoculation, 
so unavoidable for the establishment of medical science. When it 
is realized that without the results obtainable by such work — -Ex- 
perimental Pathology — millions of people must forever be threatened 
by early death from pestilence, as of old, when countless numbers 
were sufferers in these epidemics and were hurried off before their 
time and when destructive cattle plagues forced heavy burdens 
on the land, whole hecatombs of animals for which the experi- 
mentalist must account must appear but a trifling matter. Prohi- 
bition of animal experimentation, as is sought by unrestrained 
zoomania, would be equivalent to prohibiting the cure of the sick ; 
since nature affords for many affections no means for restoration 
other than the blood of inoculated animals. Human education and 
the high ethical tone of medical science will certainly be sufficient 
security that experimental pathology in pursuit of its purposes will 
not lend itself to useless animal torment. 



HISTORY OF PATHOLOGY 

Much of our experience and knowledge of the diseases of man 
and of the lower animals has come down to us from antiquity. The 
gift of observation and the faculty of reasoning, as well as his 
desire to restore impaired health, impelled primitive man to formu- 
late some kind of ideas regarding the origin and nature of disease. 
And as the grade of individual and popular intelligence advanced 
and as experience grew in value with its transmission from genera- 
tion to generation by traditions and records, so our conceptions of 
disease expanded and our knowledge advanced, or on the other hand 
mistaken ideas took deeper hold or false notions once discarded again 
came into prominence. History informs us that for some thousands 
of years there had been attained considerable skill in the art of 
healing among the Babylonians, Persians, Egyptians, Hindoos, 
Israelites, Greeks and Romans both among the priests and in the 
hands of a special class of physicians ; and although religion and 
superstition, mysticism and philosophical speculation had much in- 
fluence over it, medicine really was possessed of a very notable fund 
of information. 

In the fourth and fifth centuries before Christ considerable work 
was done by physicians and naturalists like Alkmaeon (B. C. 540), 
Hippocrates II, the son of Heraclides (B. C. 460-375) and Aristotle 
(B. C. 384-323) in the line of dissection of animals for inference 
to the supposedly similar structure of the human body, human 
cadavers being but rarely obtained for purposes of dissection. Dis- 
semination of the knowledge of medicine which existed was ad- 
vanced by the great schools of learning, like the Museum and 
Serapeum in Alexandria with their magnificent libraries (700,000 
rolls of papyrus in the Museum and 300,000 in the Serapeum), and 
by the profuse literature of the Greeks and Romans. To some 
extent, doubtless, veterinary medicine shared in this, being- practised 
both by the general physicians and by a special class of veterinarians, 
known as mulom.edici, hippiatrcs (twiros, horse; iarpos, physician), 
kteniatres {kt^vos, domestic animal ; larpds, physician) and veterinarii ; 



Early History. n 

yet in a large measure it remained in its primitive condition in 
the hands of shepherds and farmers. 

At the beginning of our present era medicine was chiefly domi- 
nated by the teachings formulated by Hippocrates and Aristotle 
in their general writings. The study of comparative natural 
science, instituted by Aristotle, laid the foundation of our 
knowledge of animal biology, of comparative anatomy and physi- 
ology; while Hippocrates and after him the physicians of his 
school established pathology. At that time it was held that there 
were in the animal and human body four cardinal humors, "blood, 
mucus, and yellow and black bile.'' It was taught that a proper 
relationship between these (crasis) insured health; and that dis- 
ease depended upon the occurrence of lack or excess of one or 
other, that is upon some modification of their relationship (dys- 
crasis). Next to the blood, the principal vital humor, Hippocra- 
tes placed mucus in order of importance, because it is often dis- 
charged in large quantities from the nose and was thought to 
come from the brain and to escape through the ethmoidal open- 
ings. Yellow bile was often seen in vomit ; but black bile was 
entirely a product of the imagination and was supposed to arise 
in the spleen. The basis of vital phenomena was supposed to 
be the inspired air (pneuma, the breath of life), which was 
thought to contribute warmth to the body. In conformity with 
the accepted theory of corruption of the humors, therapeutic 
measures were directed to a riddance from the system of the ma- 
terial which had caused the "dyscrasia ;" and for this reason 
evacuants, diaphoretics, diuretics and venesection played an im- 
portant part in those times. The importance which Hippocrates 
ascribed to these fluids or humors led to the application by later 
generations of the name Humoral Pathology to this system. 
The solid structures of the body were not entirely disregarded, 
but only vague ideas prevailed in relation to them. There 
was a theory (Democrites) that the solid parts were made up 
of particles known as atoms, between which there were pores 
[for the passage of air and humors], that the width of these 
pores varied with the varying density of deposition of the 
atoms, and that by some such method the state of the body was 
regulated. To this extent, therefore, there was a Solid Pathology, 
which, however, found but few adherents. Efforts toward 
such theoretical explanations found support particularly in the 
schools of philosophy ; and tenacity of such views and the rigid 



12 History of Pathology. 

adherence to authority, together with constant seeking after the 
keenest dialectic in argument, gave to one school of physicians 
of the day the character of "dogmatists ;" while others discarded 
entirely speculative reasoning and called themselves "empiricists," 
boasting that their methods of practice were based entirely on 
experience. They rejected the study of anatomy as superfluous ; 
in which, however, the dogmatists, although essentially bookmen 
and theorists, made some progress. 

In the middle of the second century Claudius Galenus (born in 
Pergamon, Asia Minor, A. D. 131 ; educated in Smyrna, Corinth 
and Alexandria, and afterwards practicing his profession in Rome ; 
died A. 'D. 206), noted both for his discoveries and as a prac- 
titioner, revolutionized medical science by his efforts to harmonize 
the prevailing theories with practical experience and thus give 
them a real value, and by his work in the establishment of ra- 
tional scientific methods through comparative anatomy and ex- 
periments upon living animals. Throughout the middle ages, even 
into the fifteenth century, the theories of Galen, whose discoveries 
were numerous and whose extensive writings contain much that 
is of descriptive value, were held in esteem and respect, par- 
ticularly his opinions upon anatomy and physiology. 

Through studies of this character at the hands of physicians 
a close relationship developed between veterinary medicine and 
human medicine; but there were other influences which aided in 
the development of comparative pathology. Agriculturists, like 
Xenophon, Cato, Columella, arid Virgil, and veterinary specialists 
who in Roman times attained an independent standing, and 
among whom should be mentioned Apsyrtos (circa 290-350, 
A. D.) and Publius Vegetius Renatus (circa 540, A. D.) as es- 
pecially distinguished, there were collected and recorded in litera- 
ture their experiences with various diseases, especially epidemic 
affections among animals. Although there is much useless em- 
piricism included in the dissertations of these writers, there are 
also no little excellence of observation and soundness of thought; 
and the works of the last-named author, like those of Galen, 
served for centuries as valuable sources of information. 

The general collapse of the sciences after the fall of the 
Roman Empire, during the time of migration of the European 
peoples and the period of the Middle Ages, resulted in a long 
stagnation in medicine. Practically all that is worth considering 
was the preservation of the writings of the ancients, for which we 



Middle Ages and Modern History. 13 

are chiefly indebted to the monks, working as copyists in the 
monasteries. Technical medical skill made scarcely any note- 
worthy progress. With the founding of the universities in the 
thirteenth to fifteenth centuries, when a resumption of anatomical 
investigations gradually became possible, and with the discovery 
of the printing art, which stimulated the translation and wide 
dissemination of the works of Grecian and Roman authors, there 
began a new epoch. The luminous works of the human anato- 
mists like Vesalius, Failopius and Eustachius, the experimental 
researches of Servetus and Columbus Cesalpinus, and particularly 
William Harvey's (1578-1658) discovery of the true conception 
of the circulation of the blood, led directly to the recognition of 
the errors in Galen's system and to a reorganization of medical 
science.* As usual pathology again fell into error, ascribing, un- 
der the influence of prevailing views in natural science, the 
various processes of disease and their causation now to this, now 
to that physical or chemical factor. Speculative hypotheses took 
precedence of actual experiment, and attempts at proper explana- 
tion were quite lost in the fancies of the individuals. Some were 
followers of the "chemical school" founded by Sylvius, and en- 
deavored to explain every fault by chemical changes in the com- 
position of the body, as the introduction of "sharps" (Boer- 
haave) ; others, the "neuropathologists," when the importance of 
the nervous system became recognized, laid stress upon the in- 
fluence of the nerves (William Cullen), or upon the effect of 
"stimuli" and the irritability of the tissues (the theory of ex- 
citability of Haller and Brown). Others, basing their views upon 
mechanics, believed the vital phenomena of morbid disturbances 
depended upon mechanical faults of relationship ("mechanical 
school," founded by Santoro, 1561-1635, Borelli, 1608-1677). 
Still others spoke of "vital spirits" circulating in the body, of 
"forces," of the power of the "entities" (Paracelsusf ), or made 
some injury to the immortal soul the real principle of disease 
(G. E. Stahl, 1660-1734). These doctrines were denominated vital- 
ism and animism. Such ideas have found adherents even as late 
as within the nineteenth century, clothed usually in high-sounding 
foreign verbiage to make the greater impression. 

Along with these speculative theories, however, exact clinical 

•Compare Elchbaum, Geachiohte der Heilkunde: Berlin, Pareys' Verl., 1886. 

tTheophrastus Bombastus, whose proper name was Paracelsus, distinguished 
different forces, an ens astrale (power of the stars), an em naturalc, epirituale, 
veneni, etc., as factors In life and disease. 



14 History of Pathology. 

observation, physiological experimentation and anatomical dissec- 
tion grew more and more toward a plane of real excellence, af- 
fording an increasing clearness of insight into the processes which 
obtain in both healthy and diseased bodies. The anatomical 
changes shown in necropsies directed attention to the topography 
of disease. Morgagni (i 682-1771), a teacher of anatomy in 
Padua, in his work, <c Dc Sedibus et Causis Morborum" (1761), 
outlined the first comprehensive and systematic exposition in this 
direction and came to be regarded as the founder of pathological 
anatomy. From efforts to correlate manifestations of disease of 
the various organs with the presence of anatomical changes, arose 
the school of Pathological-anatomical Diagnosis, to which is due 
the discovery of a number of valuable methods of diagnosis (per- 
cussion, thermometry, the microscope, chemical analysis), and 
which had as its founders men like Bichat, Pinel, Corvisart, 
Dupuytren, Auenbriigger, Laennec and Rokitansky. 

The advances in physiology inaugurated by Johannes Miiller 
(1801-1858) and the cellular theory formulated by Th. Schwann, 
along with the development of microscopic anatomy, are respon- 
sible for an important change from the older conceptions of dis- 
ease, giving us as a basis for our ideas of morbid processes a 
cellular pathology, first proposed by Rudolph Virchow (1858), 
who referred the real seat of disease to the individual cells and 
the tissues, and regarded disease as depending upon the reaction 
of these to harmful influences. Although it is but about fifty 
years ago that Schonlein's school looked on disease as some sort 
of living thing of extra-corporeal origin, entering the bodies of 
men and animals like a parasite and expelled by our therapeutic 
measures ; yet in the interim the study of JEtiology has developed 
the definite view that disease is but the manifestation of mor- 
phological, chemical and functional changes which are induced by 
the most varied harmful influences upon the cells and tissues, 
chemical or physical ; and thus to-day, through uniform and ex- 
act methods of objective research, clear conceptions and. positive 
knowledge are in hand relative to most diseases. 

As far as comparative pathology is concerned, it too was com- 
pletely dormant from the fourth until the eighteenth century, at 
first because of the general depression in science, later because 
medical practitioners had but little interest in the diseases of ani- 
mals when human medicine was developing along these newer 
lines, but especially because of the aversion which men came to 



Comparative Pathology. 15 

hold for even mere contact with the dead bodies of animals. 
Among the rare publications appearing in the middle ages there 
is only one large work on the anatomy of the horse (issued in 
1598 by the Venetian senator, Carlo Ruini, but probably the 
product of some physician) which is at all worthy of note as 
showing any advance in knowledge. At the same time the nat- 
ural history of the domestic animals was considerably advanced 
by C. Gessner (15 16-1565) and Aldrovandi (1522- 1605). Prac- 
tice of veterinary medicine was relegated more and more to far- 
riers, executioners and butchers and naturally drifted into the 
crudest sort of empiricism. However, when skill in riding and 
horses became more prized in the courts of princes and in war, 
there was a change for the better; and Italian, French and Ger- 
man masters of the stable (Pignatelli, Marx Fugger, Bohme, 
Winter von Adlersfliigel, Robertson, J. von Sind, Solleysel, Pluvi- 
nel, Lafosse) published a number of works upon the diseases of 
the horse. From the eighteenth century physicians once more be- 
gan to frequently pay attention to animal pathology ; the necessi- 
ties arising from devastating epidemics among cattle, particularly 
cattle plague, stimulating the members of the medical faculties 
to endeavor to stamp out these diseases and to publish numerous 
articles upon investigations bearing in this direction (Ramazzini, 
Lancisi, Schroeck, Golike, Kamper, Sauvages, von Haller, Paulet). 
In the years from 1762- 1790, in most of the [European] 
states, schools of veterinary medicine were established, the first 
being inaugurated by Bourgelat in Lyons and Alfort. With this 
step comparative medicine found a place in scientific institutions, 
later, after various changes in organization, assuming the rank of 
independent colleges or becoming incorporated with the universi- 
ties. 

The first teachers of veterinary medicine were for the most 
part physicians ; and even to the present the progress of the sci- 
ence is in close sympathy and relation with human medicine. 
However, the men who in the nineteenth century have been edu- 
cated to the dignity of independent investigators and to a new 
standard as veterinarians, have broadened comparative medicine 
to a many sided field ; and the results of their discoveries and 
their practical achievements have become of importance not only to 
the farming and cattle-raising industries, but to the general wel- 
fare of mankind as well when one takes into consideration the 
consumption of meat and the dangers of animal epidemics. 



PREDISPOSITION TOWARD DISEASE 

Any living being becomes affected by disease when no longer 
able to adapt itself to its environment and to the demands to 
which the functional ability of its cells and organs is subjected. 
As soon as such external influences exceed the limits of endur- 
ance, as soon as they so affect the cells and organs as to induce 
alteration of function, they become causes of disease. There is 
really nothing upon which the animal body is dependent or with 
which it is related, but may on occasion cause the onset of 
disease — nutriment, air, light, temperature, the various animal 
and vegetable organisms about it, the varied accidents of nature, 
its own active and passive relations, as well as every physiological 
process going on in its economy; and the very same factors, 
which are generally essential for the maintenance of existence 
and the well-being of the individual, may become agencies of 
harm and noxious (nocere, to harm) influences productive of 
disease. 

Whether the individual should experience the harmful possi- 
bilities of such factors or not depends upon the inherited po- 
tentiality of the organism, the functional capabilities of its cells 
and tissues, and upon the efficiency of its protective and reg- 
ulative mechanism. Sensitiveness to noxious influences, known 
as Predisposition, and insensitiveness or insusceptibility, commonly 
spoken of under the terms Resistance or Immunity, are by nature 
widely different among different species and individuals and even 
among the different tissues in the same animal; and are subject to 
considerable variations and abnormalities. The polar bear, the 
Esquimau dog and the reindeer are accustomed to the cold of the 
north, but sicken in the. temperature of warmer climes; many ani- 
mals thoroughly adapted to the tropics, perish when transferred to 
cooler regions even though furnished with their usual food. Indi- 
vidual animals of the same species often manifest differences of 
susceptibility, as where in herds of cattle or even, as is often ob- 
served, in a number of cattle kept in the same stable, some path- 



Variations in Predisposition. 17 

ogenic influence equally operative upon the whole group fails 
to produce its effect upon all, certain individuals resisting it suc- 
cessfully ; or it is often noticed that here and there an animal 
sickens under conditions quite favorable for most of its species. 
The difference between different tissues in predisposition and im- 
munity may be seen in comparing the skin and mucous mem- 
branes. The surface of the skin, with its hard epithelial cover- 
ing, is much less sensitive to irritative substances than are the 
delicate mucous membranes ; the mucous membrane of the stom- 
ach in the living animal is resistant to the action of acids, but 
that of the lower end of the intestinal tract may be injured by 
the acid of the gastric juice. 

A number of poisons (snake venom, tetanus toxine) are en- 
tirely harmless when taken into the alimentary canal ; although, if 
introduced by way of lesions of the skin into the tissues, they 
are extremely pathogenic. 

Especial interest attaches to the differences in predisposition 
and immunity toward the viruses of infectious diseases. In all 
infectious diseases we have to deal with poisonous materials 
caused by micro-organisms. These micro-organisms (micro- 
phytes, vegetable microscopic organisms; micro zoa, animal micro- 
scopic organisms) gain entrance to the body by alimentation, or 
by the respiratory path, or through wounds, or may even actively 
penetrate the tissues should they be in close relation with the 
skin or mucous surfaces. Within the body structure they mul- 
tiply for a time and work harm to the tissues chiefly by the 
specific poisons existing in their protoplasm (that is, in the bodies 
of the microbes) or by poisons elaborated bv them, diffused in 
the tissues and taken up by the blood. In the contest waged 
with these microscopic foreign invaders a twofold task is set for 
the animal body ; it must in the first place destroy the microbes 
and at the same time must render their toxines inert. One ani- 
mal may accomplish this with ease ; another with difficulty. Some 
species of animals are by nature uninfluenced by the toxine of an 
infection which is sure to produce disease in another species; 
thus cattle are immune to glanders, the horse to pulmonary 
tuberculosis, and chickens bear large doses of tetanus toxine with- 
out injury to health. 

Such absence of reaction to infections and their toxines in an 
animal species is spoken of as natural immunity. It is to be 
explained from one standpoint by the idea that the cells and tis- 



18 Predisposition and 1 m in unity. 

sues of the immune animal have no affinity, or but little affinity 
(chemical affinity), toward the toxincs of the infection. The 
poisonous elements simply do not enter into combination with 
them. For example, the nervous system of the turtle is absolutely 
immune to the toxines of diphtheria and tetanus, and these sub- 
stances may be injected into the animal entirely without effect. 
Yet the toxines thus introduced may remain in the bodies of the 
experiment animals for months without being rendered inert by 
the juices ; and should the blood of such a turtle be injected into 
some susceptible animal it will act in the same manner upon the 
latter as would the toxine itself. 

From a second point of view it is to be recognized that im- 
munity may depend upon the fact that some of the cells of the 
animal in question are able to take up and digest micro-organisms, 
and thus render them harmless (Phagocytosis). This power of 
seizing and ingesting small particles, organic and inorganic, or 
dead and living cells, is peculiar especially to the motile types of 
leucocytes (wandering cells, white blood cells), but is also 
possessed by giant cells, splenic and medullary cells, and even 
fixed connective tissue cells (as endothelium) ; and plays an 
important part in the economy of the body. Its significance has 
been pointed out especially by the ingenious investigations of 
Metschnikoft, Leber and Bordet. These phagocytes act as scaven- 
gers, taking up and making away sometimes with blood debris, 
nuclear fragments, pigment, fat globules and all sorts of minute 
foreign particles with which they come in contact. The ingestion 
of such corpuscular elements is with them a simple process of 
feeding. The movement and approach of the phagocytes may 
be induced by a number of stimuli, as warmth or an acid, acting 
upon their own tactile or chemical sensitiveness. In coming in 
contact with foreign particles they attempt to increase their 
surface of contact as much as possible [applying their protoplasm 
more and more about the surface of the particle, and thus 
eventually enveloping it in their own material] : and are at- 
tracted by various chemical substances (chemotaxis) . [It is 
but fair to add here that while the theory of chemotaxis, as a 
part of the general theory of "tropisms" or of blind automaton- 
like response of living things to external forces or attractions, 
finds wide adherence among medical men and biologists, there 
are nevertheless others who do not accept such a view, the latter 
rinding reason to believe that the manifestations which the former 



Protective Substances. 19 

school attribute solely to non-intelligent attraction from without 
are really due to an inherent power of a low intelligent char- 
acter of the organisms showing them. These latter would 
attribute even to individual cells as the phagocytes, a low but 
actual volitional power to either originate or refrain from efforts 
to approach the foreign particles referred to.] The proto- 
plasm of the phagocytes apparently can secrete digestive juices 
[there is reason to think that certain granules seen in leucocytes 
are of the nature of ferments], through the action of which 
they are able to assimilate nutritive matter and dissolve foreign 
bodies. 

In this latter manner, in part at least, it is possible that the 
virus of infectious diseases may be removed from the tissues. 
Nuttall first pointed out that in the blood plasma of healthy ani- 
mals there exist certain substances which are capable of dissolv- 
ing the body matter of bacteria, and of thus destroying them. 
These substances, called alexins by Buchner, and complements by 
Ehrlich (by others addiments and cytoses), are products of the 
cells, which are either given off by the living cells (Buchner) or 
are set free by cellular destruction (Metschnikoff) ; and are 
found in varying amount in the circulating blood of the indi- 
vidual animals. An excellent example of these substances is seen 
in the effect, discovered by Behring, of the serum of white rats 
upon the anthrax bacillus. If hundreds of thousands of anthrax 
germs are placed in some serum from a white rat (at 37 ° C.) 
it will be noticed after ten or fifteen minutes that the bacilli 
have become swollen and degenerated (granular), and after 
from four to seven hours that they have completely dis- 
appeared. Canine or ovine serum does not possess this power, 
but should a few drops of rats' serum be added to sheep serum 
the bactericidal action will immediately appear. The serum of 
the horse also has a strong bactericidal power. It must be clear 
that the cause of natural immunity cannot be attributed to the 
bactericidal action of the serum alone, for both rats and horses 
are susceptible to anthrax ; it must be thought of, as already men- 
tioned, as dependent in part upon the lack of affinity of the living 
cells for the toxines of the infection, and in part upon their 
phagocytic power. 

Just as among different animal species and individuals there may be 
some one kind which is more highly resistant to poisons than the rest. 
so there may be met others exhibiting" an excessive susceptibility to such 



20 Predisposition and Immunity. 

influences. For example, cats are extremely sensitive to carbolic acid. 
It is well known that some persons possess so marked a susceptibility tc 
a number of substances and foods (as strawberries, mushrooms, crabs, 
lobsters, cocoa or alcohol) that after partaking of them they experience 
severe pain, vomiting and cutaneous eruptions, and in the same way are 
apt to be severely affected by certain medicaments (chloroform or mor- 
phine) ; they are influenced by such substances, as it were by poisons. 
Such extreme susceptibility is known as idiosyncrasy (tStos, •peculiar; 
i] avyKpao-is, combination). 

As a rule, the predisposition or immunity of individuals is 
only a relative one; that is, it is variable and of moderate degree, 
may be increased or decreased, and is often only temporary. 
Racial or specific immunity may also be but relative. Rabbits 
are ordinarily immune to symptomatic anthrax, but now and 
again a rabbit is found to be susceptible to this disease upon 
inoculation. Goats, horses and cattle are strongly resistant to 
swine-erysipelas, but if large amounts of the virus are injected 
intravenously they may show severe symptoms. Young dogs are 
somewhat susceptible to anthrax ; older dogs less so. Young 
sucking calves are very rarely affected by "black leg" and usually 
resist inoculation tolerably well ; but as soon as they begin to 
eat vegetable food they become very susceptible to the disease 
in question. Thus age and food are seen to have an influence 
upon predisposition and immunity. How intimately connected 
the latter factor is may be inferred from the experiment, origi- 
nally performed by Feser and afterward confirmed by others, in 
which rats, if fed upon meat alone, are found as a rule to be 
immune to anthrax, while if fed on bread they soon succumb to 
inoculation with the virus. 

By experimentation it has been shown, moreover, that hunger 
is a predisposing cause, that bodily overexertion (overheated ani- 
mals), nutrition of restricted quality and excessive amount ( as a 
diet too rich in fat) may have such depressing influence that 
animals subjected to them readily succumb to injurious agencies 
which they would otherwise bear, and particularly become less 
resistant to infections. It is also true that certain altered condi- 
tions of the tissues afford especially vulnerable points for the 
attack of pathogenic influences ; for example, gastric catarrhs, by 
diminishing the production of hydrochloric acid, favor the 
deposition and pathogenic action of bacteria which are otherwise 
destroyed by the gastric juice. As a rule, previous disease leaves 
as a sequel an increased disposition, the formerly affected tissues 



Acquired Predisposition and Immunity. 21 

showing a diminished resistive power for a long time {local pre- 
disposition; locus minoris resist entice) , as, for example, mucous 
membranes after catarrhs. 

Predisposition to disease and (a matter of extreme impor- 
tance) immunity against disease may be acquired. It is well 
known that recovery from certain infectious diseases is accom- 
panied by an insusceptibility to a repetition of the same affection. 
This immunity after previous attacks is at times only temporary, 
but a few weeks or months in duration, or it may extend over 
many years or for the entire lifetime. The alteration which has 
taken place in the condition of the body in such cases is chiefly 
a chemico-biological one, and although much remains enigmatical 
concerning it, some insight into the process has been obtained 
through experimental investigation. Besides the discoveries of 
Jenner and Pasteur, who gave to mankind facts and methods of 
the highest importance toward success in combating infections, 
by which it has become possible by artificial inoculation of an 
attenuated virus to produce a mild course of the infection and to 
obtain therefrom immunity from subsequent attacks of the same 
disease, there must also be recalled the important discovery that 
in the blood of man and animals, after attacks of infections, there 
appear certain substances which are of specific anti-toxic char- 
acter and are destructive to the virus, and that upon the produc- 
tion of these substances depend protection and recovery from these 
diseases. The tissues of the animal body react to irritants which 
gain access to them. Should a particle of dust or a gnat happen 
to lodge upon the conjunctiva, such a foreign body acts as a 
stimulant to the nerves of the mucous membrane, this inducing a 
free secretion of tears, which usually wash away or dissolve the 
object. In an analogous manner there is a reaction on the part 
of the tissues should a toxine or some pathogenic germ (virus, 
bacterium) come into contact with them, not in this case with a 
simple secretion to wash away the poison, but nevertheless re- 
straining the poison and giving origin to substances which are 
apparently actual antitoxines, or which are able to destroy and 
thus render harmless the germs of disease. The conditions un- 
derlying the production of such antagonistic or protective sub- 
stances, their mode of origin, manner of action and properties, are 
of extremely complex nature. The numerous experiments of such 
investigators as Behring, Ehrlich, Brieger, Kitasato, Wassermann, 
Buchner, Emmerich, Fodor, Nuttall, Nirssen, Bordet, Morgenroth 



22 Predisposition and Immunity. 

and Sachs, have, however, brought forward facts hitherto unsus- 
pected and of the greatest interest in this connection, and have 
pointed out not merely theoretical hypotheses upon immunity, but 
also practical methods of extreme value in combating the in- 
fectious diseases. 

As already pointed out, there already pre-exist in the normal 
blood of every animal certain substances capable of dissolving 
foreign material which has in some way gained entrance, and, by 
entering into combination with resultant toxic matter, of render- 
ing it harmless. In some of the glands, as the thyroid and liver, 
neutralization of toxic matter and noxious metabolic products is 
being continually carried on; and when one considers the innu- 
merable reactions ; and interactions which are taking place in 
metabolism, resulting in the most varied types of secretory ma- 
terial with destructive and digestive properties, it is easy to think 
of the body and each of its cells as a chemical laboratory of 
manifold productive ability. 

In attempting an explanation of the mechanism involved in 
the production of these antibodies (antagonistic or protective 
substances), Ehrlich has proposed a brilliant, and, at first thought, 
a very convincing theory, the chief points of which are briefly 
included in the following. The hypothetical details of this theory 
have recently met such serious objection at the hands of Gruber 
that in a great measure it seems but doubtfully credible. The 
basic fact that antitoxines and protective substances are products 
of the cells and organs of the body is not endangered by this 
criticism, but the problem of how and where such substances are 
formed is renewed as a matter for further investigation. 

According to this view the cells of the body may be thought 
of as organisms which consist of a basis of protoplasm, which 
has as its vital center a nucleus (vital nucleus of Ehrlich) ; 
this protoplasmic unit may be fancied as being possessed about 
its periphery of armlike processes, the receptors or side-chains of 
Ehrlich. [It is to be understood here that the author refers to 
the protoplasmic molecules as the basis of this theory, each mole- 
cule being composed of a more or less complex group of atoms 
or of combinations of atoms. The vital center does not refer to 
the nucleus seen as a structural part of the cell, but to the struc- 
tural nucleus of such a complex molecule of its protoplasm. As 
is attempted in the graphic chemical formula of a complex or- 
ganic molecule with the symbol C as its center, to indicate as 



Ehrlich's Theory of Immunity. 23 

"side-chains" the various atoms or groups of atoms linked 
about this nucleus, so in Ehrlich's view the living proto- 
plasmic molecule may be thought of as having as its elemental or 
basic compound a vital nucleus about which are attached, and 
probably from which spring, a number of other atomic groups 
subsidiary to the center of the molecule and corresponding to the 
side-chains of the formula, but essential to the efficiency and 
integrity of the whole complex molecule, since they are its means 
of combination. These are the receptors or haptophores of the 
molecule. Every molecule possesses these haptophores in addition 
to its principal part, the centre or nucleus (in living protoplasmic 
molecules, the vital centre). Should these haptophores be lost in 
the living molecule, they are replaceable by others of like type 
because of the vital regenerative power of the molecule.] 

The receptors are the principal instruments of [molecular, or 
in other words] intracellular metabolism and provide nutri- 
tive substance to the cells through their ability to unite chemic- 
ally with such material. However, just as proper food elements 
may thus combine, so other albuminous bodies or materials chem- 
ically allied to foods become linked to or combined with the 
receptors, as material extracted from bacteria, various poisons 
of animal, bacterial and vegetable origin (toxines, venom of bees, 
spiders or snakes, diphtheria toxine, ricin, abrin, the substance 
of blood cells, spermatozoa and nervous tissue, and the milk 
albumen of different kinds of animals). Such union occurs be- 
cause these substances contain in their molecular composition 
certain groups of atoms, which, like similar atomic groups in 
foods, have an affinity (chemical affinity) for the atomic groups 
of the cellular protoplasm ; these Ehrlich speaks of as their 
haptophore groups. [Thus both the protoplasmic molecules of 
the body cells are provided with haptophores or combining chains, 
and, too, all nutritive or harmful molecules which come in con- 
tact with them. Should there be affinity between the haptophores 
of the cellular protoplasm and those of the introduced molecules a 
combination will result.] With such combination effected 
[the molecule and in proportionate degree the whole] cell comes 
under the influence of the substance chained to it. Should 
the latter possess properties actively harmful to the protoplasm, 
poisonous qualities (toxopHore), the cellular protoplasm becomes 
more or less injured, and a pathological cellular lesion results. 
There may ensue complete death of the cell [protoplasm], 



24 Predisposition and Immunity. 

or merely a condition of irritability or partial injury. If the 
injury be partial that part of the cell [protoplasmic molecule] 
which remains sound restores the defect. In this condition of irri- 
tability or stimulation there is a reaction on the part of the cellular 
protoplasm left with its vital centre intact to regenerate the 
receptors destroyed by the toxic influence. Following a law 
recognized by YYeigert, regeneration in the cells of an organism is 
usually productive of more of the substance than originally ex- 
isted at the site of loss ; and so here the restoration is often so 
active that an excessive number of receptors are supplied to 
replace those which have been destroyed. "Such an excess of 
receptors constitutes a useless ballast for the cells and the extra 
ones are thrown out into the blood and circulate therein" (Ehr- 
lich, YYechsberg). The presence of these free receptors in the 
blood, representing haptophores or chemically combining sub- 
stances, affords opportunity for materials which have gotten into 
the blood and which have chemical affinity for them, having come 
in contact, to enter into combination with the receptors. Thus 
held by these free receptors, such substances are prevented from 
involving the cellular protoplasm, and as a result the cells and 
the whole individual are protected from the disease. 

This power of molecular combination differs in the different 
cells of the same individual and in the cells of different species 
of individuals. One species may possess no cells containing the 
elements essential for combining with a certain toxine ; th£re 
would then be absolutely no chemical affinity shown between the 
cellular molecules and the toxic molecules, and a priori the latter 
must be without effect. In such a case the toxine, perhaps in 
large quantities, may remain for weeks in the blood and general 
circulation without any harm resulting to the individual. Such 
instances are examples of natural immunity. On the other hand, 
an individual may possess a vast number of receptors not merely 
in the general body, but each cell, each corpuscle, for example, 
may contain a mass of material capable of combining with sub- 
stances of one or other kind. In classification of these receptors 
it is customary, following Ehrlich, to distinguish them as of 
I. II. III. etc., orders. 

The first order (uniceptors) includes receptors having only 
one haptophore group for poisons (toxines) and utilizing this for 
combination with such substances ; they are called antitoxines. 
The presence and formation of antitoxines is illustrated by the 



Lysins. 25 

immunity to toxines acquired after infectious disease. The tox- 
ines are allied to the albumens* and enter the blood in a state of 
solution; thus dissolved, they here enter into combination and are 
therefore inert before they gain access to the tissues, as the nerv- 
ous tissues — the cells (bacteria) which give origin to the toxines 
being removed from the economy by phagocytosis (as tetanus or 
diphtheria bacilli). 

Another class of receptors [III order of Ehrlich] has the 
power of combining with foreign cellular elements and at 
the same time drawing into the combination the ferment-like 
alexines which naturally have pre-existed in the blood; these 
thus must possess two haptophore groups (a cytophile and a 
complementophile group), and for this reason are known - as 
amboceptors. For this element which is the medium (amboceptor) 
of the chemical union (anchoring together) the following terms 
are also employed; desmon (s&*> = I bind), immune body, 
intermediary body, copula, immunisin, Hxateur, sensitising body. 
The alexine is also known as the complement, addiment and 
cytose. When by the combined action of these two elements the 
destruction and solution of foreign cellular elements (the toxine- 
producing animal and vegetable microorganisms themselves) are 
accomplished, the compound antibody [amboceptor and comple- 
ment] is spoken of as a cytolysin (E. S. London). The 
presence of the two elements allied to each other is shown by 
experiment. If one will heat a serum containing cytolysins to 
56 C. the complemental element will be destroyed, and the 
serum will be found to have lost its cytolytic power, is inert. If, 
however, to this serum there be added another, ordinary serum, 
containing only complement and inert by itself, the cytolytic 
power is restored to the first, and it is said to have been 
reactivated. So, too, the desmon or amboceptor in the cytolysin 
may be removed by adding to serum cells for which it has 
affinity [and by centrifugation these may be thrown down ; while 
the serum continues to contain the complement]. There are 
a number of cytolysins of different kinds, each exerting its 
influence as a rule upon only one certain kind of cell [this 
depending upon the peculiar affinity of the amboceptor in the 
cytolysin combination] ; thus we recognize among many 
those which act upon red blood cells (hemolysins), upon sperma- 

*Poisons of other typos, alkaloids, glucosldes, saponinos, which do not act bj 
forming chemical combination do not cause the formation of antltoxlnes In the 
organism. (Ehrlich, H. Sachs.) 



26 Predisposition and Immunity. 

tozoa (spermolysins) , upon bacteria (bacteriolysins) , upon white 
blood cells (leucolysins). Some dissolve several kinds of cells, as 
in the case of spermolysins, which destroy red blood cells as well 
as spermatozoa. From this it may be seen that in general 
cytolysins possess specificity of action. 

The appearance of cytolysins in the body of any given animal 
is occasioned by the introduction of cells of a different species of 
animal into the first. If human blood be injected in increasing 
amounts under the skin of a rabbit or into its peritoneum, the 
serum of the rabbit will acquire the power of dissolving the hu- 
man red blood cells, but not those of horses, cattle or guinea-pigs. 
If the spermatic fluid of guinea-pigs be introduced into rabbits, 
in the same way the serum of rabbits becomes solvent for the 
spermatozoa of guinea-pigs, but cannot influence the spermatozoa 
of another species of animal. If colon bacilli be injected into an 
animal a cytolysin will be developed destructive only to these 
microphytes, and in fact only to the particular strain of this 
bacterial group which was employed in the experiment. 

From the foregoing it should be realized that the principal feature 
in the production of immunity against foreign cellular elements is the 
formation of the amboceptor or desmon, and that this alone is a new 
product of the cells of the invaded body ; the other element, the alexine, 
naturally pre-exists in every body, its combination with the desmon form- 
ing the cytolysin. If, however, the necessary alexine be absent or present 
in insufficient amount, the cytolysin will not appear. In this latter way must 
be explained such occurrences as where, in spite of repeated introduction 
into an animal of some type of cells, the blood acquires no cytolytic power, 
but where on further addition of the serum (containing the required alex- 
ine) from another species of animal cytolytic activity is immediately 
produced. 

The sources of the amboceptors are apparently the bone- 
marrow, spleen, lymph glands and perhaps the subcutaneous con- 
nective tissues. 

In addition to the production of antitoxic and cytolytic sub- 
stances the body may engage along the same line of reaction 
in the formation of substances [II order of Ehrlich] which 
cause foreign cells to aggregate in masses (clumping, agglutina- 
tion), the so-called Agglutinins ; and other substances which 
coagulate foreign types of albumens (Coagnlins) and cause their 
precipitation (Precipitins). In illustration, if defibrinated human 
blood be injected into a rabbit there is developed in the blood 
of the latter a substance which will act on human blood to 



Post-Infectious Immunity. 27 

cause a flocculent precipitate, but which will not (as a rule, and 
never if certain modes of application are employed) exhibit such 
precipitating qualities with any other type of blood. It is inter- 
esting in this connection to add that the serum of a rabbit so 
treated will also precipitate the blood of anthropoid apes, gorillas, 
orang-outangs and chimpanzees, thus indicating a relationship of 
these animals to man. Cytolysins and hemolysins also serve to 
show the relationships existing between animals in the zoological 
system of classification. Inasmuch as this reaction is applicable 
as well with a solution of old and dried blood, the discovery 
(which as an outcome of research in the field of immunity is due 
particularly to Bordet, Ehrlich and Morgenroth) has acquired 
especial importance as a means of information concerning the 
source of blood stains in forensic medicine. 

Other albumens may also lead to the formation of specific 
antibodies in the animal organism, as milk albumen ; thus by 
subcutaneous injection of goat's milk into rabbits, horses or cows 
a serum may be obtained which will immediately cause a precipi- 
tate if it be added to goat's milk. In the same way, by inocula- 
tion, coagulins may be obtained for cow's milk. 

In the same way, too, in the course of an infectious disease 
a series of substances are produced in the human or ani- 
mal organism which render the infectious matter for the time 
harmless. Should the infectious products develop very rapidly, 
and by their poisonous properties cause serious protoplasmic 
changes in the body cells, the disturbance is apt not to be limited 
or checked, and in spite of any reactive-products which may be 
formed the function of the cells becomes altered and the animal 
dies. Should the [protoplasmic molecules of these] cells be only 
partly injured the body prevails over the disease, the molecular 
defects of the cells becoming regenerated. The surplus of anti- 
bodies, the result of this regenerative action, are after recovery 
found circulating in the blood, and in some instances may even 
pass into the milk. The amount of protective bodies or anti- 
bodies in the body-fluids varies according to the intensity of the 
reaction and the time elapsed after recovery from the infection, 
the greater part being used up during the course of the disease 
and the remaining gradually disappearing in metabolism ; while 
with the removal of the stimulus the supply from the cells tends 
to cease. If, however, infectious and toxic material be again 
introduced into the system, stimulating and injuring the cellular 



28 Predisposition and Immunity. 

protoplasm, the production of antibodies will be again induced, 
receptors being again formed. This form of immunity, produced 
through cellular activity following the introduction of the infec- 
tious agents, is known as "active immunization." The discovery 
of the existence and production of specific antibodies in the serum, 
for which we are mainly indebted to the studies of Behring upon 
tetanus- and diphtheria-immunity, has led to extremely im- 
portant methods of prophylactic and therapeutic inoculation against 
a number of the infectious diseases. This becomes possible from 
the fact that the blood serum of an animal which has survived a 
certain infection and is highly immunized against it can be em- 
ployed by injection to produce in a second animal similar im- 
munity against the same disease. The production of the pro- 
tective material in the blood depends upon the introduction into 
the experiment animals, either intravenously or subcutaneously, of 
gradually increasing amounts of the infectious material against 
which immunization is sought. The animals in this way become 
more and more highly immunized and their blood serum becomes 
correspondingly rich in antitoxine. By such a system of pro- 
gressive inoculation it is possible to attain a degree of concentra- 
tion in which a thimbleful of the serum contains more immuniz- 
ing material than would exist • in all the blood of the body after 
one single attack of the disease. The ability to produce such 
materials exists in the cells of all kinds of animals, both those 
susceptible to the disease in question and those naturally resistant 
to it. For example, by injecting the bacilli of swine-erysipelas, 
which in natural conditions are pathogenic only to the bristled 
kine, it is possible to induce the reaction also in sheep, goats, 
cattle and horses and produce in their blood immunizing substances ; 
and then, after withdrawal of the blood from animals ' thus pre- 
pared, to obtain from it a prophylactic and curative serum in suffi- 
cient quantity for use in hogs. , The production of active im- 
munity in an individual requires some time, because the body cells 
must first form the protective substances ; in other words, must 
first pass through the period of the disease, perhaps four to six 
weeks in duration. When, however, the prepared serum is intro- 
duced there is no such demand placed on the body cells; the pro- 
tective substances, already formed, produced from the animal 
supplying the serum are introduced into the second animal. An 
immunity thus obtained is spoken of as "passive immunity." It 
conies on immediately or in a few hours after the inoculation. 



Protective Immunization. 29 

according to circumstances. As a definite cellular reaction in 
such a case does not occur at all, or at best only in a minor 
degree, and as the amount of protective antitoxic material intro- 
duced is gradually used up, destroyed or excreted (urine) and 
no new antitoxine is afforded because of lack of proper reaction, 
such passive immunity passes away after a short time (seven to 
fourteen days). 

The recognition of this peculiarity has in practical application 
led to , the coincident or successive employment of both methods 
of immunization in case of certain of the infectious diseases. 
Serum is first injected so as to induce a passive immunity in an 
animal, and living germs are next inoculated so as to transfer a 
passive into an active immunity ; the previous introduction of the 
protective serum making the later inoculation with living microbes 
practically free from danger. 



CONGENITAL AND INHERITED DISEASES 

If there exist at time of birth in an individual actual disease, 
or peculiarities of predisposition or immunity which also char- 
acterized the parents or ancestors, such conditions are said to be 
congenital (innate), and in the latter instance inherited (heredi- 
tary) as well. The genesis of such an occurrence is by no means 
always the same, although in a measure it is apparently dependent 
upon conditions of the parents. 

During intrauterine life the embryo may experience injuries 
affecting its normal growth, causing deformity, interfering with 
the proper development of a limb or organ, or destroying some 
part already in stage of development. Such injuries are for the 
most part mechanical in type, as where amniotic adhesions (or 
more rarely tumors of the uterus) by constriction or pressure of 
this or that part of the foetus (which in its movements might be 
entangled in the amnion) may compress, wound or otherwise 
injure it. Depending on the nature of such an injury, the embryo 
may in consequence present gross or trivial faults of one sort or 
another; these are spoken of as foetal or embryo genoits anomalies, 
vitia congenita, developmental defects or monstrosities. Except 
when a uterine lesion is the cause of the deformation of the foetus, 
the mother has no influence upon the production of anomalies in 
the offspring. 

There are a number of infectious diseases whose causative 
micro-organisms are capable of gaining access to the foetus indi- 
rectly through the placenta. In .their multiplication in the pla- 
cental tissue they may, by growth, penetrate it and obtain entrance 
to the blood of , the foetal side. Under such circumstances the 
newly born animal carries into the world with it the same disease 
from which the maternal parent was suffering during the term of 
her pregnancy; the acquirement is here placental. The most com- 
mon example , of such a transmission is seen in congenital tuber- 
culosis in cattle, occurring only in case the cow has uterine tuber- 
culosis. The congenital pathological conditions of this type have 



Congenital Predisposition. 31 

therefore an intrauterine mode of origin, which, if strictly inter- 
preted, is comparable to acquirement by an external influence, only 
that in this instance it operates within the womb. 

It is reasonable to believe that injurious metabolic products 
which pass through the placenta of a mother animal suffering 
from some febrile condition (especially metabolic and nutritive 
disturbances which react from the mother upon the embryo, 
affecting primarily the ovum, or in the father's case affecting the 
spermatozoon in a similar manner) occasion morbid predisposi- 
tions, as diminished developmental energy, or perhaps a tendency 
to excessive growth (dwarfism, foetal chondrodystrophy, gigan- 
tism), weak metabolic power, tendency to fatty degeneration or 
fatty deposition (ovo genie or spermato genie predisposition, con- 
genital degenerative inheritance). 

According to Weissmann and Ziegler, it is quite probable that 
often predisposition to disease and congenital pathological char- 
acteristics are due to germinal variations ; that is, that when two 
unadapted sexual cells unite there may be developed to some de- 
gree new and perhaps even abnormal peculiarities in the embryo 
from the union of the two elements (amphimixis of the 
ovum and spermatozoon). Thus healthy, strongly-constituted 
parents may often be seen who sometimes beget offspring of 
feeble constitution, weak-minded or of other morbid tendency. 
The offspring is never entirely like either parent, and the various 
members of the same generation are never alike in bodily struc- 
ture and character. Only in case of twins, developing from one 
ovum or from one act of copulation, is there striking similarity of 
the bodily features. In the mingling of the maternal and paternal 
sexual elements two strains of hereditary tendency unite to pro- 
duce new germinal variations. Should there be thus produced 
new peculiarities of value to the individual, or which we care to 
preserve, type-characteristics (precocity), these are not regarded 
as pathological ; but it is readily conceivable that the variations 
might but poorly fit the offspring for life and render it but feeblv 
resistant to given pathogenic influences or show from the first 
abnormal constitution of its tissues. In such cases is presented a 
germinativc or constitutional predispositio)i. 

A predisposition, no matter how developed, as well as ac- 
quired immunity, may be transmitted to the offspring, provided 
the individual is capable of begetting; yet not every tendency 
toward disease and not all the resistive powers of the parent are 



32 Heredity. 

necessarily continued to succeeding generations. Only such con- 
ditions are transmitted as pre-existed in the germ, in the seg- 
mentation cells and the embryo, or those in which apparently the 
nature of the whole parental cellular structure is altered, as 
germinal variations and so-called constitutional tendencies and 
diseases. * 

Injuries and diseases which do not involve the sexual cells, as 
all simple traumatic lesions of the body, give rise to no trans- 
mission. For example, the common custom of cropping the ears 
and tails of dogs has never led to the birth of a short-eared or 
stub-tailed dog or of such a breed (just as the practice of cir- 
cumcision, practiced for hundreds of years among various peo- 
ples, has never yet caused any congenital anomalies of the 
prepuce). If occasionally structural anomalies of this type are 
encountered careful investigation will show that some intrauterine 
mechanical fault is responsible for the defect in the foetus, as 
Bonnet has demonstrated in case of stump-tailed dogs that the 
caudal vertebrae have been bent or deformed simply by intra- 
uterine pressure (amnion). This is also proved by the fact that 
the same anomaly occurs in cats (and in any other animals whose 
tails are unobjectionable to man and for the removal of which 
there is no occasion), showing that the habit of cropping can 
scarcely be held responsible. 

Non-transmissible conditions and those which are truly in- 
herited may very closely resemble each other in their anatomical 
features, and yet depend on entirely different causes ; only the 
closest inquiry revealing the fundamental influences producing 
them. For example, supernumerary toes (polydactylism) may be 
an atavistic phenomenon, a family trait, or may occur in a foetus 
as a splitting of a digit because of amniotic adhesions ; in the 
same way harelip (congenital fissure of the lip) may be caused 
by local amniotic trauma or may be an hereditary anomaly.* 

Heredity is best understood when it concerns chemical in- 
fluences. As indicated by Ribbert, it may be conceived that the 
whole body can suffer from the wide dissemination through it of 
some chemical substance and that, of course, under the circum- 
stances the germ cell is also reached by the same noxious ma- 
terial. If the organism survive such disturbance and become 
immune through the changes called forth by the chemical poison, 
the germ cell may also survive with the same immunising changes. 
Should such a process befall both parents, both spermatozoon 



Hereditary Disease. 33 

and ovum are likely to be immune and the new cellular structure 
resulting from the copulation of these two (the embryo) will 
possess the same characteristic and transmit it again, because 
its own sexual cells are clearly the descendants of the rest of 
the group. In the same way a predisposition may be established 
and transmitted, because the chemical substance in some way 
weakens the germ cell and diminishes its resistive ability, and by 
the fusion of two similarly enfeebled sexual cells the progeny, as 
the product of both, partakes of their qualities. Similarly to 
such chemical influence as Ribbert suggests, any exaggeration 
or diminution of the body temperature must affect the germ 
cells. 

Inherited pathological conditions and properties of immunity 
need not necessarily manifest themselves in each successive gen- 
eration of posterity indefinitely ; for the most part they are 
limited to a few generations and then disappear. But they may 
recur in later generations. If but one of the progenitors possess 
a certain predisposition and come in sexual union with a non- 
predisposed individual, the pathological condition will progress- 
ively diminish by half (Ribbert) because of its distribution in 
the two sexual cells ; is proportionately corrected by the healthy 
cell of the copulation and by germinal variation ; and grows 
weaker and weaker until it is no longer a factor in the posterity. 
Should the peculiarity reappear after several intervening genera- 
tions, it may be assumed that this occurs as a result of the union 
of two germ cells, each possessed beforehand of a disposition 
which was hitherto latent, but which from the summation of the 
characteristics of both parent cells has again become sufficiently 
intensified to reappear as a pathological fault (Ribbert). Hence we 
distinguish : a direct heredity from father and mother to the off- 
spring; a latent heredity if the offspring of affected parents are 
spared but in the next or later generations the disease should appear, 
arising from a transmitted tendency; a collateral heredity, should 
the disease manifest itself in the side lines of the family group ; 
an atavistic heredity, when the origin of the disease suggests a 
reversion to the family ancestry. 

In human medical practice the following are considered as 
diseases transmissible by heredity : Haemophilia or hemorrhagic 
diathesis, color blindness or Daltonism (so named after the 
Englishman, Dalton, who was himself color-blind), lenticular 
opacity or "gray cataract" (or cataract), near-sightedness or 



34 Heredity. 

myopia, pigment-atrophy of the retina, polyuria (production of 
excessive amounts of urine), predisposition to mental diseases, to 
progressive muscular atrophy, to tumors, to obesity and to cer- 
tain malformations (dwarfism, polydactylism, harelip, etc.). The 
anomalous conditions mentioned are due, perhaps, to germinal 
variations, possibly first brought into active manifestation by 
the introduction of some external disturbing factor. (Vide Rib- 
bert, Lehrbuch der allgem. Pathologie. 1901.) 

What parts respectively are taken by heredity and by external 
influences in the development of congenital affections is in many 
instances difficult or even impossible to determine, as our knowl- 
edge of these matters is still deficient. This is particularly true 
regarding the so-called hereditary defects of the domestic animals. 
Among the diseases included in this category for the last century 
or more, some are surely not inherited and not transmissible but 
occur because of external influences ; for example, intermittent 
ophthalmia, cataract, asthma, ringbone, frog-thrush. Others, as 
dumb-staggers ["blind-staggers"], hsemoglobinsemia, curb, spavin, 
deficient hoof-formation, may be caused directly by external in- 
fluences, although it cannot be denied that inherited structural de- 
fects may indirectly favor their appearance.* As instances of 
direct inheritance and congenital origin may be mentioned many 
cases of goitre in animals. 

*Cf. Dieckerhoff, TJeber d. Erbf elder bei Zuclitpferden: Zeitschr. f. Veterindr- 
kunde, 1902, Feb., p. 53. 



CAUSES OF DISEASE 

The influences which lead to bodily injury, to pathological 
lesions, and which are spoken of collectively as disease causes 
(causes morbi) may be arranged in a number of classes. 

There are influences against which the strongest and most 
resistive constitution is powerless and which inevitably induce 
disease in the animal coming under their action; such absolute 
pathogenic influences include mechanical forces, intense thermic 
and electric agencies, mineral and vegetable poisons in their 
higher dosage and concentration, and, provided they can gain 
entrance to the intracorporeal structures, various animal para- 
sites, bacteria and [animal] microorganisms. Other harmful 
agencies are pathogenic only under special circumstances and 
are therefore only relative, depending, for example, on the 
quantity of the exciting agent, or upon special predisposi- 
tion of the subject or upon the concurrence of several harmful 
influences (relative causes of disease). The occasion which brings 
a harmful influence in relation with the body or subjects the 
latter to such influence, is spoken of as the predisposing cause 
(causa proximo). The principal factor in producing a lesion is 
known as the special, immediate or essential cause of disease 
(causa essentialis) ; among these it should be understood that 
either external harmful agencies which have gained entrance into 
the body or which operate upon it from without, or some already 
existing tendency toward disease may be included. For example, 
pasturing upon some upland infested with anthrax affords the 
opportunity by which the anthrax bacillus as the essential cause 
of anthrax gains entrance to the body; an injury, the favoring 
condition for wound infection by the essential cause of tetanus. 
Anything which promotes the action of an injurious agent may 
be regarded as a contributory cause (causa au.vilians). 

Pathological influences may be divided into the following 
groups : 



36 Causes of Disease. 

1. Disturbances of Nutrition and Alimentation: Abnormal 
states of nutrition depending on irregularity in the water or nutri- 
tive elements afforded. 

2. Obstructions to Respiration: Interferences with oxygen 
convection. 

3. Functional Disturbances: Depending upon fatigue, upon 
overexercise of the organs. 

4. Thermic Influences: High or low temperatures. 

5. Electric Agencies. 

6. Mechanical or Traumatic Agencies. 

7. Chemical or Toxic Agents: Poisons. 

8. Microbic or Infectious Agents: Micro-organisms belong- 
ing to the protophytes and protozoa. 

9. Animal Parasites: Of the class of worms and arthropoda. 

Disturbances of Alimentation and Nutrition. 

Total deprivation of food without water supply (complete in- 
anition) leads, in case of the higher vertebrates, to rapid loss of 
body-weight, emaciation and death in the course of from one to 
four weeks. With absolute rest (as in case of imprisonment in 
a caved-in mine) an adult man may retain life without food and 
drink for about twenty, days; exertion hastens the end. Strong 
dogs have lived under similar conditions for thirty-six days ; 
horses and cats should live for about four weeks with absolute 
rest. Guinea-pigs and rats die within three to nine days. Liberge 
states that a well-conditioned cow, which had wandered into an 
out of the way place and had remained there forty days without 
food and without opportunity for much exercise, picked up 
quickly on a milk diet and was in tolerable condition eight days 
after being set free. 

If water is obtainable abstinence from food can be endured 
without permanent harm by man and carniverous animals for 
from two to four weeks, and the fatal end may be postponed for 
a considerably longer period. A cat experimented on by Bidder, 
weighing two and one-half kilograms, died on the eighteenth day 
from starvation after having lost 1,197 grams (water consumed, 
131. 5 grams). Birds of prey (eagle) endure hunger and thirst 
for twenty to twenty-eight days ; small birds only two to nine 
days. Mascagni has recorded a turkey's having fasted for twenty- 
nine days. In case of cold-blooded animals the requirement for 
food is so small that water-salamanders and turtles may live for 



Disturbances of Nutrition. $7 

a year, snakes for six months and frogs for nine months, taking 
nothing but water. 

When fasting an animal must furnish whatever energy is 
necessary for the maintenance of its proper temperature and for 
its organic functions (muscular activity and circulation) by the 
destruction of its body tissues, nourishment from external sources 
being impossible or insufficient. How the destruction of tissues, 
an actual self-combustion, takes place and how the vital organs 
live upon the less important structures, is well shown by the com- 
prehensive studies of E. Voit. Fat and glycogen are first sacri- 
ficed, and as long as these substances are present the albuminous 
elements are not subject to the destructive process, the muscular 
structures afterwards bearing the greatest part of the loss. Loss of 
weight and atrophy are most marked in the omentum and the 
fleshy parts (also the fat and glycogen stored in the liver), and 
fat animals succumb to starvation later than lean ones Accord- 
ing to Chossat, young, poorly nourished pigeons die after three 
days with a loss of one-third their body- weight ; plump ones after 
thirteen days, with a loss of half their weight. The heart shows 
the least loss in weight (its constant activity and functional stimu- 
lation hindering its atrophy) ; the central nervous system similarly 
loses but little, and the diminution in the red corpuscles is com- 
paratively unimportant. (Lipomata are unaffected in starvation; 
attempts to cause their removal by starvation have been un- 
successful. — Samuel.) Death from starvation takes place after 
the development of great muscular weakness, with complete loss 
of power and deep stupor (Samuel). In the bodies of animals 
dead from this cause are to be noted muscular and glandular 
atrophy, passive congestion and degenerative changes, together 
with scanty contents of the small intestine and diminished lumen 
of the latter. 

Complete inhibition of water (as in feeding with material arti- 
ficially deprived of its water) acts quite as effectively as hunger, 
death taking place in from eight to twelve days. Animals, un- 
able to quench their thirst, refuse food, and the organism is unable 
to adequately supply the fluid secretions necessary for digestion. 
Death probably is due to the retention in the system of injurious 
metabolic products (with poisonous qualities), which cannot be 
flushed out. Actual drinking of water may very well be avoided 
by a number of animals (rabbits, guinea-pigs, cats or parrots) 
without injury to health, provided the food ingested contain water. 



38 Causes of Disease. 

Diminution in the amount of food ingested, undernutrition 
(relative or incomplete inanition), is often met with in connection 
with diseases of the alimentary tract; its consequences are pre- 
cisely similar to those of total withdrawal of food, save that the 
progression of the case is slower. Usually the condition is ac- 
companied by a diminution of erythrocytes in the blood {inanition 
ancemia), tbe alimentary disease producing wide disturbance 
through fluid-waste (diarrhoea) and other complications. 

Faulty composition of food causes partial starvation, the body 
suffering loss in its fat, albumen or carbohydrate should its nour- 
ishment lack or contain but an insufficient amount of one of these 
substances, or should the animal by preference and exclusively feed 
upon only one of these types of nutritive material. Impoverish- 
ment of the diet in such manner brings about emaciation and 
physical weakness. If lime should be deficient in the food and 
water supply the skeleton will fail of its most essential constituent, 
that which gives it its rigid strength, and the bones become soft. 

Respiratory Faults. 

All animals die by asphyxia* if their supply of oxygen be 
prevented. A wide range of factors may bring about a diminu- 
tion in the proportion of oxygen contained by the blood, asso- 
ciated as a rule with insufficient separation of the carbonic acid 
and its consequent high proportion in the blood. Primarily this 
may result from the insufficient access of atmospheric air to the 
respiratory organs, as by closure of the superior orifices [smoth- 
ering] or by obstruction of the respiratory tube [choking] 
and constriction of the latter (strangulation, compression of 
the larynx or trachea) by fluids and foreign bodies (the latter 
also by lodging in the pharynx and occluding the trachea), pres- 
sure upon the larynx and trachea by tumors, obstruction by 
tumors or swelling of the mucous membrane in the folds of the 
glottis or in the bronchial tubes, collections of blood, fluid or 
coagulated exudates in the lungs and bronchi. 

A second group of asphyxiating causes includes interference 

•The editor is here taking the liberty of using the word asphyxia as the 
general term, including smothering as meaning respiratory obstruction, operative at 
the respiratory orifices, mouth and nose- : choking, respiratory obstruction operative 
within the mouth, nasopharynx or oesophagus (pressing on the larynx or trachea) ; 
strangulation, respiratory obstruction by constriction or pressure from without 
upon the larynx or throat generally; suffocation, respiratory obstruction by any 
type of cause operative below the level of the larynx, either within (as a suf- 
focative gas) or without (as pressure upon the chest). In English this meaning 
is attached to asphyxia, although as Prof. Kitt indicates In the present section 
it really means pulseless; his own general term is "Erstickung." 



Respiratory Disturbances. 39 

with the respiratory movements, as in case of rupture of the 
diaphragm, the principal muscle of respiration, in case of its 
immobility or when it is forced forward by flatulence, in case of 
marked pressure from without upon the chest walls (animals 
standing pressed together in railway cars), or in case of pressure 
upon the lungs by large fluid collections in the chest cavities. 
Failure of respiratory movement may also occur from nervous 
origin (pressure upon the brain, paralysis of the vagi, spasm of 
the bronchial muscles). Premature separation of the placenta or 
compression of the umbilical cord in the maternal canal prevents 
oxygen convection to the foetus. 

Furthermore, passive congestion of the lungs, interference 
with the emptying of the pulmonary veins and hsemic changes in 
which the blood corpuscles have lost their ability of taking up 
oxygen (carbon monoxide poisoning) render diffusion of the 
gases so difficult that the same result of lowering oxygenation 
arises, and the respiratory disturbance eventually advances to the 
stage of suffocation. The presence of irrespirable gas and the 
reduction of oxygen in the air of an inclosed space (instead of 
20.8 per cent., perhaps only 2 to 3 per cent.) act in a similar 
manner. 

In one or other of such a variety of ways asphyxia may be 
the termination of a number of diseases and is the commonest 
cause of death. It is usually accompanied by the symptoms 
of dyspnoea (?y M<ncvoia, from wiw, difficult breathing, shortness of 
breathing), labored respiratory movements (suffocative dyspnoea), 
marked increase in the cardiac movements, spasmodic twitching of 
the general musculature and loss of consciousness. 'Toward the close 
the respiratory movements become irregular, sometimes intermit 
and suddenly cease, the inspirations occasionally becoming very 
deep (terminal respiratory movement) ; and the spasms weaken 
the cardiac action (true asphyxia, actual pulselessness, from 
d privitive and 6 <r<i>vyfj.6s, the pulse). When the diminution in 
oxygen is gradual in its onset these symptoms appear less promi- 
nently ; but as the tissues degenerate from the insufficient supply 
of oxygen (fatty degeneration of the heart, liver, kidneys) and 
as the respiratory nervous center loses its excitability, the patient 
dies from gradually increasing loss of consciousness and cardiac 
failure. According to the rapidity of onset of the fatal end and 
the causes of the asphyxia, the post-mortem findings present dif- 
ferent pictures. In addition to the local changes due to strangn- 



40 Causes of Disease. 

lation, obstruction to the respiratory passages or the rest of the 
causes mentioned, the most common features of this mode of 
death are found in the tar-like, uncoagulated, dark condition of 
the blood (excessive presence of carbonic acid, deficient decarboni- 
zation) and in the presence of haemorrhages in the lung and 
pleura. 

Excessive Functional Stimulation. 

All organic activity is accompanied by consumption of the 
essentially functionating material of the organs and by the 
formation of metabolic products. Both of these factors, especially 
the accumulation of the latter substances in the tissues of the 
organ, lead to a gradual reduction in efficiency, that is, to fatigue. 
This is normally corrected (restoration or reconstitution of the 
part) during the intervals of rest, when the accession of arterial 
blood replaces what has been lost and the lymph current sweeps 
out the waste products (fatigue waste). Should the various or- 
gans be required to continue their activity without intervals of 
rest for a long time, or should they suddenly be overstrained, 
or called into functional effort beyond their physiological ability, 
their parenchymatous substance may be so affected by the height- 
ened metabolism and so marked an accumulation take place of 
the waste products of fatigue (carbon dioxide, phosphoric acid, 
either free or combined as acid phosphates), that exhaustion or 
wearing out results, with complete abolition of functional ability. 
This condition is clearly pathological if tissue changes can de- 
velop in the process and make the loss of function permanent 
(fatty degeneration or cellular atrophy), or if the cessation of 
function, momentary though it be, can cause in the vital organs 
disturbances involving the general economy or the actual death 
of the individual. 

Coincidence of other contributing causes (the weakened stage in 
fevers, traumatism or thrombosis) favors the development of such 
functional lesions from overexertion, as seen especially in the 
heart, the general muscles and in the nervous system. 

General muscular fatigue and cardiac exhaustion may be 
the cause of death in overheated animals. Horses suffering from 
thrombosis of the abdominal aorta and its branches exhibit signs 
of functional disturbance of the muscles of the posterior limbs, 
even under moderate effort, because of their poor arterial supply 
and the accumulation of waste products from fatigue.' The heart 



Functional Stimulation; Thermal Influences. 41 

fatigued by prolonged effort may lose its power of contraction to 
such a degree that it becomes abnormally distended by the pres- 
sure of the contained blood (cardiac dilatation, insufficiency of 
the heart), with ensuing disturbance of the circulation. Over- 
stimulation of the nervous system by sudden psychical shock is 
not only in man productive of serious results ; fright palsy with 
cessation of cardiac action (paraplexis) has also been observed 
in the lower animals (fowls). 

A gradually and only moderately increasing demand upon the 
muscles and glands acts as a stimulus to their functional activity, 
provided proper nutrition be afforded the tissue, and results in func- 
tional hypertrophy, that is, in an increased growth of the cellular 
elements corresponding to the demand for work. This may be 
noted especially in tubular structures provided with muscular 
walls (smooth muscle), where there is gradually and spontane- 
ously developed an increasing competence for the work required 
of the muscle, as in the thickening of the muscular layers of the 
bladder in case of gradually narrowing stricture of the urethra 
(v. functional hypertrophy). 

Thermic Influences. 

High temperature of the surrounding atmosphere (above the 
body temperature peculiar to the animal) may lead to failure of 
heat loss (heat stasis) and hyperthermia of the entire body with 
fatal termination by so-called heat-stroke. This is frequently ob- 
served in hogs when crowded in railway cars. The condition is 
most easily induced if the dissipation of the body heat by evapora- 
tion is diminished, and at the same time heat production in- 
creased in the animal by prolonged muscular effort or by rich 
feeding. (It is known from experiments that warm-blooded ani- 
mals kept in well-ventilated warm chambers at 36 to 40 C. 
die, some in from one to three days, others in from ten to thirty 
days. The body temperature of such animals — rabbits — rises to 
39 to 42 C. ; they become dyspnceic and there is increase in 
the frequency of the pulse ; the haemoglobin of the blood is re- 
duced, and degenerative changes develop in the heart, the liver 
and kidneys. — -Ziegler.) The cause of death is cardiac failure 
(heat rigidity) occasioned by the overheated blood, or may de- 
pend upon a thickening of the blood through excessive loss of 
fluid by sweating and respiration (fall of blood pressure, dimi- 



42 Causes of Disease. 

nution in vascular tone). As anatomical changes are found red- 
dening of the skin (in hogs), failure of blood coagulation, dilata- 
tion of the right heart, venous hyperemia of the lungs, liver, 
kidneys and brain. The names insolation and sunstroke are ap- 
plied to that form of heat-stroke which is caused by the influence 
of the direct heat-rays of the sun upon the body, particularly 
upon the head; it is thought to depend upon a paralytic dilatation 
of the vessels of the meninges and cortex of the brain, and the 
affection is accompanied by convulsions and marked symptoms of 
excitation (Birch-Hirschfeld). 

The influence of heat locally applied occasions lesions known 
as bums (combustio) , of various grades according to the 
degree of temperature, the duration of application and the resist- 
ive powers of the tissues to heat. Burning may result from con- 
tact with solid, liquid or gaseous heated matter, or from direct 
action of a flame or radiant heat. Short exposure, to a tempera- 
ture of 40 to 50 , or longer exposure to 30 to 40 C. is pro- 
ductive of an inflammatory reaction marked merely by dila- 
tation of the capillaries (hyperemia) and redness of the part 
(inflammatory burn, erythema, burn of the first degree or of mild 
degree). The process is only superficial, leading at most to 
desquamation of the epithelium. Exposure to heat of 60 to 8o° 
C. (burn of the second or intermediate degree) is productive, 
in addition to the hyperemia, of rapid exudation of serous 
fluid from the dilated vessels beneath the epithelial layer. The 
cells of the stratum Malpighii are pressed apart by this, become 
swollen, are loosened from the papillary bodies, and the firm, 
horny portion of the epidermis is raised up to form a blister. 
Through minute fissures, easily made in this bleb, pyogenic 
bacteria may enter, the fluid contents through further exuda- 
tion [leucocytes] becoming turbid and purulent. Should the 
blister rupture the hyperemic papillae beneath are exposed, the 
repair of the epidermis starting from the epithelium at the mar- 
gins of the lesions or from remnants of the Malpighian cells 
which were not destroyed. In case of mucous membranes, which 
are devoid of the horny epithelial layer, blister formation is not 
likely to take place, the epithelial layer desquamating in shreds ; 
and the denuded surface is covered by a coagulating exudate, the 
so-called croupous or false membrane. The more severe influ- 
ences of heat, above 8o° C. (bums of the third degree), 
produce searing and charring (eschar formation) ; the burned 



Thermic Influences. 43 

tissue coagulates ; the blood within the capillaries is coagulated 
and stagnant, the tissue dying in consequence and being trans- 
formed into a brownish crust (or eschar). At the border of the 
actually involved and necrosed tissue inflammation ensues. Heal- 
ing follows by the separation of the charred material and the 
formation of scars, which are apt to be of a radiating, reticular 
appearance, and which by their contraction and shrinkage may 
cause considerable disfiguration. All these degrees of burning 
may coexist as the heat has happened to influence in a greater or 
less measure one or more places. 

In extensive burns of the skin (if as much as one-third of 
the body surface is involved) the subject is likely to die, even 
in case of burns of no more than the first or second degree. 
Death may take place within but a few hours after the occurrence 
of the accident with symptoms of impaired respiration, cardiac 
weakness and fall of the body temperature. In other cases the 
fatal end may take place after the course of a week, during which 
there may have been apparently favorable progress, pulmonary 
cedema and nephritis often developing in the meantime. Other 
cases pursue a course of some weeks' duration before the lethal 
end. The explanation of the dangerous features and fatal termi- 
nation of such burns is to be sought ' in part in functional dis- 
turbance of the skin in heat dissipation, fall of blood pressure, over- 
heating and inspissation of the blood (cardiac paralysis) and in 
part by the changes which the blood corpuscles undergo. Dif- 
ferent investigators (Salvioli, Maragliano, Castellino, Ponfick) 
have shown by experiment and observation upon human cases, 
that after burns of the skin the red blood corpuscles, partly de- 
generate (broken into small particles) and partly without any 
apparent structural changes, are incapable of conveying oxygen, 
and give up their haemoglobin (partly changed into methcemoglobin) 
into the serum, whence it is excreted by the liver and kidneys ; 
that, further, the formation of hyaline thrombi is apt to take 
place and that these alterations of the blood may be regarded as 
the cause of death. 

Low temperatures, which deprive the body of its proper 
warmth, may give rise to either local or general disturb- 
ances in warm-blooded animals. Sensitiveness to the power 
of withstanding cold varies very much in the different animal 
species. Fishes chilled to the freezing point may seem to be 
lifeless, their lymph frozen into solid ice ; yet they may com- 



44 Causes of Disease. 

pletely recover from such a condition. Frogs are said to remain 
viable for hours subjected to a temperature of -2.5 C, with the 
heart frozen solid (anabiosis). 

According to Koch, resuscitation is possible only by gradual thawing 
and providing only a part of the water present in the body has been 
actually frozen; in case of rapid thawing, violent diffusion currents appear 
between the water emerging from its crystalline form and the concentrated 
albuminous solutions of the bldbd and tissues, which may destroy the 
tissues (Koch, Ziegler). 

Hibernating animals sleep but lightly with a blood temperature 
of 6° C, but soundly at i.6° C. ; their cardiac beats sink to eight 
to ten each minute; breathing is almost suspended, the movement 
of the lungs caused by the heart action alone carrying on the 
feeble gas diffusion in the lungs (Samuel). 

The hair and feathers (especially the winter pelt) of animals 
lessen the loss of heat by radiation and by convection of the 
[warm] air from the surface of the body ; in consequence 
of which animals are seen to endure with ease the ordinary cold, 
providing they are well nourished, move about freely and thus 
produce heat abundantly. [The loss of this protective element 
or the presence in the hair of much moisture favoring the ready 
convection of the heat from the body surface reduces tremen- 
dously the power of resistance to cold; and one finds the cattle 
in the prairies freezing to death in a rain at a temperature con- 
siderably above ice-forming temperature, although were the hair 
dry and capable of holding the layer of warmed air close to the 
skin the animals would have shown no signs of discomfort.] 
If there be diminution of heat-production because of insufficient 
nutrition, and extreme cold, even well-pelted animals (hares and 
deer) and birds may be frozen to death. Death by freezing takes 
place by loss of sensibility of the nervous system, with fall of 
body temperature, diminution in the frequence of the cardiac 
and respiratory movement, cerebral anaemia, loss of muscular 
power and blood coagulation. 

The local action of cold, varying with duration of exposure 
and intensity, causes tissue changes of the same types as in 
burns (frosting, congelation). Primarily there results a constric- 
tion of the vessels of the part exposed (local anaemia), after 
which, if the cold continue, the nerves and muscle tissue of the 
vessel walls become paralyzed and dilatation of the vessels ensues 
with increased blood content, this condition usually returning to 



Thermic Influences. 45 

normal when the low temperature of the part is corrected. Tem- 
peratures below the freezing point are, however, likely to so 
disturb the vessel walls that inflammation of the tissue (swelling 
and redness of the skin, frostbite, chilblain) develops with or 
without the formation of blisters"; or after especially long and 
severe exposure the blood and lymph circulation cease and the 
tissue dies as a result. The necrotic area may be separated from 
the normal by inflammatory reaction, or if it remain moist may 
undergo putrefaction through the influence of invading bacteria. 
The extremities • are the parts of the body most commonly sub- 
ject to freezing, but it is seen rather seldom among animals, for 
example, the scrotum in bulls (Bang), the paws in dogs, in 
horses the thick skin of the hoof, particularly the crown and 
pastern. Jewsejenko and Cadiot have recorded instances of 
necrosis from freezing of the deeper part of the foot in horses 
(in the Russo-Turkish and Franco-German wars, as well as in 
Algeria). 

By the term catching cold (chilling) is meant the pathogenic 
action of heat loss not sufficient to cause freezing, but produc- 
tive of functional disturbances and inflammation of nerves, 
muscles, joints and internal organs. The laity commonly and 
primarily for almost all affections attributes chilling as the cause ; 
and even the physician often evades the question as to the origin 
of some malady with the vague phrase of the possibility of catch- 
ing cold, because of the obscurity of the aetiology of the case. 
Many diseases formerly regarded as produced by exposure to 
cold are now recognized in the advanced state of ^etiological in- 
vestigation as infectious, although undoubtedly there is a group 
of affections in which chilling of large areas of the skin and 
mucous membranes may with confidence be held responsible as 
the causal agency. Such a relation is evident in cases where, after 
unusual exposure to cold (thorough soaking, strong draughts, 
falling into icy water, heat loss by radiation to some neighboring 
cold object as a stone wall) there immediately develop in the 
chilled parts pains, functional disturbances and symptoms of in- 
flammation, or where in a short time these phenomena without 
other demonstrable cause appear in the subjacent or more distant 
parts of the body. Cats almost invariably become sick if they 
become soaked by falling into the water, while flocks of sheep 
have been attacked by pleuro-pneumonia directl) after wool 
washing if, while wet, they were left exposed to cold air. The 



46 Causes of Disease. 

occurrence of paroxysms of colic (dysperistalsis) in sweating 
horses after chilling of the surface cannot be denied. Rabbits and 
guinea pigs dipped into ice-cold water have been known to 
quickly sicken and die from pulmonary and renal inflammatory 
affections. As a further illustration it is well known that the 
peritoneum is very susceptible to the effects of lowered tempera- 
ture, and that in case of extrusion of the viscera or in operations 
involving the exposure of the peritoneal cavity there often arise, 
even at a temperature of 21 ° C, entirely from the chilling (under 
conditions of asepsis and in the absence of other causes), a gen- 
eral depression of temperature, attacks of colic, peritonitis and 
perhaps a fatal termination. 

Hofer has observed that chilling may affect even fishes., provided they 
be suddenly changed from a warm water to a cold ; and that such chilling 
causes changes in the skin (desquamation and necrosis of the epithelium). 

Attempts to frame a theory explanatory of the real nature 
of chilling have as yet been unproductive of any definite informa- 
tion on the subject. If it be assumed that the blood in the 
cutaneous vessels is chilled, it remains unexplained why practi- 
cally only isolated parts of the body are affected, although the 
chilled blood flows on to other organs. Excretion of blood pig- 
ment in the urine (hemoglobinuria) after exposure to cold 
might well be explained upon the idea of chill effects upon the 
blood causing destruction of the corpuscles, yet in such cases of 
hemoglobinuria there is usually a previously developed myositis 
and the red color of the urine is looked upon as a result of the 
liberation of muscle pigment and not as depending solely on 
blood destruction. The chilling of the skin causes extensive vas- 
cular constriction and the blood is forced from the surface and 
accumulates in the internal or more deeply lying parts of the 
body. Why in these cases the blood is not evenly distributed 
in the body, but collects in special localities, is an open question. 
Sudden exposure of a cutaneous or mucous surface to cold un- 
doubtedly causes an appreciable vascular tonic contraction, which 
may be ascribed to stimulation of the vaso-motor nerves. This 
vascular spasm is not limited to the area directly affected by the 
cold, but extends consensually or reflexly to adjacent or symmetri- 
cal, or distant vascular areas (Samuel). If, for example, one dip 
a hand into very cold water the other hand also becomes paler 
(Samuel), and probably everybody has had the experience that oc- 



Thermic Influences, 47 

casionally a sudden chilling of the feet brings on directly a reflex 
sneezing and nasal catarrh. Rossbach has observed in experiments 
upon cats that by applying cold compresses over the abdomen vas- 
cular constriction passing over into vascular dilatation develops in 
the mucous membrane of the respiratory passages. There usu- 
ally succeeds upon the vascular constriction a relaxation of the 
vessel walls with which is associated a marked congestion (vid. 
Hyperemia). Such disturbances are, of course, commonly cor- 
rected, the vascular constriction and internal congestion together 
with the vascular relaxation disappearing, and the chilling is 
realized but for a short time as a sense of cold or brief catarrhal 
affection by the subject. Why the same adjustment does not 
occur in all cases is not clear. We only know as a fact that the 
chilling leaves in the skin itself practically no anatomical altera- 
tions, that the sensitiveness of the nerves, contractility of the 
vessel walls, the circulation and perspiration are entirely re- 
stored, while in the deeper structures the vascular spasm and 
the succeeding vascular dilatation are apt at times to be pro- 
longed. Sometimes, as further consequences, local engorge- 
ments, nutritive faults of the tissues, inflammatory exudates, ex- 
cessive mucous glandular secretion are to be seen ; sometimes 
catching cold may manifest itself only by nervous symptoms, 
functional disturbances and sensations of pain and may abso- 
lutely fail to give any idea concerning the anatomical changes 
of the tissues. 

Affections which arise in consequence of catching cold are 
often but transient and are very apt to change their location in 
a system of tissues, appearing successively at different points 
along the larger nerves and in muscular regions and at different 
joints. For this reason they have been called rheumatic affections. 

[While it is true, as the author indicates, that the varied 
effects of chilling of the cutaneous surface are not susceptible 
of a simple explanation, there are certain probable influences 
which can scarcely be overlooked. The development of congest- 
ive states in some mucous membrane in connection with the 
more or less widespread vascular changes beginning in the skin 
may be held as offering favorable conditions for the more active 
growth and penetration of some microorganisms, which perhaps 
in the normal condition, although present, were unable to advan- 
tageously invade the membrane, and many of the catarrhs which 
follow refrigeration undoubtedly show clear evidence of such in- 



48 Causes of Disease. 

fectious agencies. The old idea that by causing a more or less 
prolonged contraction of the cutaneous vessels the skin secretions 
are reduced or prevented and that in this way there tend to 
accumulate metabolic or other toxines in the tissues cannot be set 
aside. Such substances have been thought to perhaps possess 
irritant qualities which disturb the sensory nerves and muscle 
fibres and other structures, the rheumatic pains and stiffness sup- 
posedly arising in consequence. At least some weight is to be 
given to the readiness of disappearance of such symptoms when 
by warmth and exercise the general circulation is stimulated and 
skin secretion heightened, these toxines then perhaps finding more 
ready excretion from the body than could be afforded by the 
other excretory paths.] 

Electrical Influences. 

Powerful electrical discharges upon the animal body induce 
paralysis of the nervous apparatus (especially of the respiratory 
centre), electrolytic destruction of the red blood cells, local 
burns of the skin and laceration of the tissues. Death usually 
follows ; but the paralysis and unconsciousness may, after shorter 
or longer duration, go on to recovery. The larger animals (cat- 
tle and horses in the stall or in the open) are especially liable 
to be struck by lightning (Frohner, Ziegenbein). Contact with 
live wires and completion of the circuit through the bodies of 
horses occasionally takes place when they step upon the contact 
points of an electric railway in the street pavements or on a 
broken overhead wire.* Horses have been killed by a current 
strength of 500 volts, 100 amperes (Puntigam, Mouquet, Blanch- 
ard) ; alternating currents of 160 volts are sufficient to kill dogs 
( Birch-Hirschfeld) . 

According to Leblanc, horses are exceptionally susceptible to electricity. 
A horse was killed, for example, by a relatively light current which the 
owner passed through the bit in order to divert the attention of the animal 
while being shod. 

Anatomical changes may be entirely absent when death has 
been caused by electricity, or the hair may be found singed and 
the skin burned by the electric spark ; and at the points of en- 
trance and exit of the lightning or current, as well as in the 
internal organs, the tissues may be lacerated, with which lesions 

♦Birds sit on telegraph wires with impunity because they are not in contact 
with the earth. 



Electrical and Mechanical Influences. 49 

haemorrhages of course occur. Along the entire course of the 
current tree-like, branching lines of singeing (hyperemia and 
haemorrhages), the so-called lightning pictures, may be seen in 
the skin and intestines. In addition the blood is dark and un- 
coagulated, the muscles dark brownish-red, the endocardium 
stained by the altered blood, and the heart muscle at times the 
seat of hemorrhagic infarcts. 

Mechanical Influences. 

Pathological changes are very frequently produced by me- 
chanical force. These are either lesions of tissue cohesion, 
ruptures {breaks in continuity, Icesio continui), or of compression, 
as the constriction of a hollow organ, condensation of tissues 
or displacement of organs. If this be caused by external forces 
or foreign bodies the process is spoken of as traumatism {trauma, 
t6 rpavna, lesion, lat. Icesio). The active agent is either a dull (fall, 
blow, jolt, pressure, pull, friction) or a pointed or sharp (stab, incis- 
ing) solid body. . In the same way internal mechanical disturbances 
may be caused by adhesions of the tissues, tumors and other 
pathological products producing constricting influences, or by 
excessive blood pressure, abnormal gas expansion or pressure 
by fluids; or may involve the functions of organs (displace- 
ment of actively motile stomach, intestine, uterus or x muscle). 
If the force gives rise to loss of continuity amounting to visible 
separation of the tissue the lesion is spoken of as a zvound, 
hurt, tear {vulnus, trauma in restricted sense) ; if affect- 
ing dense structures (as bones, cartilage or teeth), as a break 
(fracture) ; if the tissue be destroyed by compression, as a crush, 
contusion or bruise. Displacements (dislocations) are met in 
joints, bones or muscles, as wrenching or luxations; in the intes- 
tines as ruptures (hernia), or twists (volvulus). The term 
stenosis is employed in connection with constriction and oblitera- 
tion of hollow organs ; where the closure is caused by some fac- 
tor in the inside of the organ it is spoken of as an occlusion 
stenosis; where it is due to external pressure it is said to be a 
pressure stenosis. 

The results of mechanical injury are extremely numerous and 
vary with the size and character of the producing agent, 
as well as of the local lesion, and with the relative importance of 
wounded tissue to the general organism. A wound is often 



50 Causes of Disease. 

complicated by other factors, as from the entrance of microbic 
or toxic agencies through" the opening or breach made by the 
foreign body, with the result of further alteration of the tissues. 
The traumatic agent may be at the same time the conveyor of 
such substances, or may itself be a living parasite. Intense 
mechanical force may sometimes without any evident lesion, 
sometimes with manifest lesion, cause serious and perhaps fatal 
effects upon the nervous system. For example, this occurs in vio- 
lent concussion of the body (commotio from com-moz'eo). espe- 
cially if the vertebral column be directly affected ('concussion of 
brain and spinal cord — the former causing the loss of conscious- 
ness, the latter bilateral palsies of the extremities, the bladder 
and rectum I . What the precise anatomical changes are which 
in such instances take place in the central nervous system has as 
yet not been determined, autopsy usually showing nothing that 
is characteristic. Possibly the alterations are molecular. 

Death sometimes takes place suddenly, too, from blows upon 
the abdominal wall and viscera. Such instances are characterized 
by sudden loss of strength, fall in body temperature, cardiac fail- 
ure and diminution of nervous excitability. This condition is 
known as shock, traumatic stupor, collapse, traumatic reflex par- 
alysis. It is thought that the paralysis and cardiac failure in 
such cases is due to vagus irritation. 



■» 



Chemical Agents: Poisons. 

Substances which harm the animal body by their chemical ac- 
tion are known as poisons; the actual process of introduction of 
the poison and its action, as poisoning or intoxication. Probably 
nearly all chemical substances can. under proper conditions, act 
as poisons, or, in other words, have a deleterious influence upon 
the tissues ; the mode and power of combination of the chemical 
and the amount and degree of concentration in which it is present 
in the body being important items. For example, a substance 
as essential for the body as sodium chloride will in large doses 
cause vomiting and fatal poisoning in dogs. The most poisonous 
substances, as hydrocyanic acid or nicotine, have absolutely no 
effect when given in the minute doses of the homeopaths. 
Changes in the relation of the atoms and solubility may 
transform a non-poisonous substance into a poisonous one and 
vice versa; of the two forms of phosphorus, only the white is 



Chemical Agents. 51 

poisonous, the amorphous red form being harmless even in large 
quantities. A number of substances which are insoluble in water, 
and which have practically no effect when brought in contact with 
the skin or when introduced subcutaneously, are changed by the 
hydrochloric acid of the stomach so as to become serious poisons ; 
for example, carbonate of barium is changed in the stomach 
into the soluble chloride of barium. On the other hand, there 
are substances which are apparently energetic poisons when in- 
troduced into the blood, but which are inert in the stomach be- 
cause they are completely neutralized by the albuminates of the 
gastric juice ( Samuel ) . 

Many poisons belong to the mineral kingdom or are artifi- 
cially made from minerals, as arsenic, mercury, iodine, bromine, 
chlorine, lead, copper and others, and the various compounds of 
these substances (oxides, sulphides, chlorates, chlorides, etc.). 
The organic compounds, as alcohol, chloroform, hydrocyanic acid, 
cyanide of potassium, carbolic acid and picric acid, especially 
[include many poisons]. 

The vegetable kingdom (Samuel) affords many examples of 
poisons. There are whole families of plants whose genera and 
species possess some poisonous principle common to them all. In 
many plants certain parts may contain a poisonous substance, 
while the rest may be quite free from it and edible (as is well 
known in case of potato plants, solanum tuberosum, whose leaves, 
blossoms, seed and immature fruit contain the poisonous solanin, 
while the tubers are quite free from it). A number of plants are 
innocuous, slightly or seriously poisonous, depending upon ques- 
tions of climate, location, character of the soil and cultivation ; 
the almond tree, for example, bears either sweet or bitter al- 
monds, according to the location. The most powerful poisons 
contained in the higher plants are the vegetable alkaloids (mor- 
phine, atropine, colchicine, digitaline, etc.). In case of the 
lower plants also, especially the bacteria, there are products, some 
of which are marvelously toxic, fatal to large animals in the 
most minute and scarcely appreciable amounts ; these substances, 
analogous to the alkaloids and enzymes, or oi albuminous nature, 
are embraced by the terms toxines, toxalbumcns, toxenzymes. 
(See also chapter on bacteria.) 

Among animals there are a number known to be able to 
elaborate poisonous secretions within special glands, especially 
the venomous snakes (vipera bcrus, the common adder of Ger- 



52 Causes of Disease. 

many; vipera Redii and ammodytes in southern Europe, the dif- 
ferent species of crotalus (or rattlesnake) in America, possessing 
poison glands in connection with the teeth or jaws. Scorpions, 
the females and neuters among honey bees, wasps and bumble 
bees possess poison glands and a sting at the posterior end of the 
abdomen ; toads and salamanders, wart-like skin glands ; hairy 
caterpillars, many biting flies, gnats and gadflies, salivary glands. 
There are certain species of fish, like the barbel, whose sexual 
glands contain a poisonous fluid and whose fins are provided with 
a poisonous substance derived from the skin glands. It is not 
certain whether the occasional poisonous qualities of edible 
mussels, oysters and star fish depend on transient gland secre- 
tions (sexual seasons), upon the food of these animals, or whether 
they arise from bacterial changes of the animal after death. 

The changes caused by poisons are partly limited to certain 
localities, partly connected with general anatomical and physio- 
logical changes.* 

The poisons may be arranged for classification in four groups, 
according to their modes of action: (i) Corrosive, locally irri- 
tative poisons; (2) Parenchymatous poisons; (3) Hcemic poisons; 
(4) Nerve and Cardiac poisons. Many do not confine their in- 
fluence to a simple type, but excite lesions and symptoms of mul- 
tiple character simultaneously. 

The corrosive and locally irritative poisons {caustica, irritan- 
tia) vary in their results with the dosage and concentration of 
application and with the character of the tissue with which they 
come in contact, ranging from simple hyperemia and inflammation 
to coagulation, eschar-formation and solution of the tissues. 
Such lesions depend upon special properties of the substances, 
as abstraction of water from the tissues, precipitation or solution 
of the albumens, formation of precipitates in mucus forming tis- 
sues, solution and decomposition of urea, conversion of fats and 
carbohydrates into acids, as well as production of a variety of 
chemical changes in the salines of the body or other destruction of 
the structure of the living protoplasm. Among these caustics and 
irritants (to the skin or mucous membranes by direct contact) 
are included the corrosive acids (sulphuric, nitric, hydrochloric, 
oxalic, osmic, acetic, carbolic, f etc.), the caustic compounds of 
the alkalies and alkaline earths (potassium and sodium hydrox- 

*The following Is taken from the works of Samuel, Ziegler and Blrch- 
Hlrschfeld. 

tCarbolic acid or phenol is really an alcohol. 



Chemical Agents. 53 

ides, quicklime, barium chloride), the corrosive salts of the heavy 
metals (salts of antimony and mercury, zinc chloride, zinc sul- 
phate, chromate of potassium, etc.), the poison of the beetle Lytta 
vesicatoria, cantharidin, snake venom, the poison of the sting glands 
of bees, wasps and hornets, the salivary secretion of gadflies, 
stinging flies and mosquitoes, and the so-called acria or acrid medi- 
caments derived from a number of plants (croton oil, mezereum, 
etc.). A number of poisons, volatile or gaseous in form, may 
also cause dermal or mucous membrane irritation, especially to 
the lining of the respiratory tract during inhalation (irrespirable 
gases). Should these irritant and corrosive substances be ab- 
sorbed and be conveyed by the lymph paths into the blood and 
internal organs, they may cause, in addition to their local effects, 
associated disturbances of the heart and nervous system, the liver 
and kidneys. Substances inducing degenerations of these paren- 
chymatous organs may be spoken of as parenchymatous poisons, 
their effects depending chiefly upon alterations of tissue meta- 
bolism, regressive nutritive changes and formation of precipitates 
in the tissues. Among this group phosphorus belongs, capable 
of causing extensive fatty degeneration of tissues, especially the 
liver. Corrosive sublimate, chromic acid, cantharidin, which pro- 
duce marked changes in the renal parenchyma, are also irritants. 
The production of argyria, the impregnation of the tissues with 
minute black particles of silver after long continued administration 
of nitrate of silver, may be thought of as a similar process ; 
and lead is an excellent example of parenchymatous poisons, 
producing, as it does, a wide range of disturbances, palsies, de- 
generations and both local and general pathological results. 

The so-called hcemic poisons act principally by depriving the 
red blood corpuscles of their power to act as conveyors of oxy- 
gen, by inducing their disintegration, liberating and breaking up 
haemoglobin or causing thrombosis. Some in addition may cause 
lesions at the point of introduction, and perhaps directly influence 
the nervous system. Some of them are gases entering the blood 
through inhalation, others are in solution and are derived per- 
haps from the intestine or from wounds. The best known blood 
poison is carbon monoxide, a constituent of illuminating gas, 
which enters into combination with haemoglobin to form carbon- 
oxyd-hsemoglobin, and thus prevents absorption of oxygen by the 
blood and induces a tissue asphyxia. A characteristic feature of 
CO poisoning is the bright, cherry-red color of the blood. Sul- 



54 Causes of Disease. 

phuretted hydrogen (in poisoning from the gas of manure pits) 
acts partly by paralyzing the nervous system, partly by forming 
sulphmethsemoglobin, giving a greenish (almost cadaveric) tint to 
the blood. Hydrocyanic acid and cyanide of potassium also cause 
a rapid paralysis of the central nervous system, in addition to 
interfering with oxygenation of the blood cells and tissues (cyan- 
methaemoglobin, bitter-almond odor in the organs). Potassium 
chlorate, nitrobenzole, potassium nitrate and amyl nitrite cause 
marked destruction of red corpuscles and transform haemoglobin 
into methaemoglobin, in which the oxygen is more firmly fixed 
than in the oxyhemoglobin. The blood, and of the organs in such 
instances the kidneys especially, take on a striking brown color. 
Extensive haemocytolysis, with liberation and solution of the 
haemoglobin in the blood plasma, giving a blood-red color 
to the urine (hemoglobinuria), are caused by various toxines 
of fungous and bacterial origin (ptallin, helvellic acid), arsenu- 
retted hydrogen, anilin, nitrous acid (fumes), carbolic acid and 
other poisons. Coagulation of the blood and its sequels are seen 
in poisoning with ricin (from the seeds of castor oil plant) and 
abrin (from the seeds of abrus precatorius). 

Infectious Agencies. 

By the term infection (inficere, to put into, to inoculate, 
to taint) is meant the entrance into the system of a disease-pro- 
ducing microorganism capable of self-multiplication, a pathogenic 
microbe. 

Nature is richly supplied with microorganisms ; which on the 
borders between the animal and vegetable kingdoms represent 
primitive forms of living matter, in their minuteness are visible 
only with the aid of the microscope and are recognizable as 
consisting of but single cells. According to their classification 
as plants or animals, they are spoken of as protophytes or pro- 
tozoa. There are forms which are only visible with a magnifica- 
tion of 2,000 diameters, and even then as barely perceptible points 
without definable cellular characters ; and there are reasons for 
believing that still smaller organisms exist, invisible with our 
present optical instruments, but by no means unreal, being dem- 
onstrated as corpuscular entities by other methods, as by their 
detention in filtration or by inoculation (so-called invisible 
microbes). 



Infectious Agents. 55 

Even in ancient times the idea prevailed that devastating 
epidemic diseases were caused by a living contagion (contagium 
vivum sive animatum). The nature of these contagions re- 
mained hidden, however, to the physicians of antiquity ; and the 
impossibility of determination led, especially in the middle 
ages, to the wildest conjectures as to the nature and origin of 
epidemics. They were attributed to evil spirits, deemed punish- 
ments from on High, fancied the results of supermundane pow- 
ers, of influences of the stars ; their origin was sought in con- 
ditions of the weather, in magnetic and meteorological processes, 
in putrid gases and in peculiarities of the soil ; and the hidden 
factor was characterized as a constitutio epidemic a or pestilens. 
It is only about fifty years that our conceptions as to the real 
nature of epidemics began to become clearer and an assured 
foundation became established by precise observation — when, with 
the aid of the microscope, it became possible to demonstrate the 
existence of low vegetable organisms as foreign and invading 
elements in the diseased body and to determine the role which 
they play in the production of disease. In the last few decades 
this phase of science, stimulated and reorganized by the luminous 
work of Louis Pasteur and Robert Koch, improved by many 
technical aids and demonstrative methods, has fully disclosed 
the developmental history of many infectious diseases. Advances 
of tremendous significance for the whole of medical science, dis- 
coveries and experiences of the greatest consequence in the com- 
bating and cure of diseases, have been attained in this line of 
study. * 

The demonstration of the relation which a given microbe 
bears to a given disease has been especially facilitated by the 
success of artificial cultivation of microorganisms outside the 
body (in vitro, upon nutritive media) and of production at will 
at any time thereafter of the infectious disease by inoculation. 
Such experiments have been made not only in animals, but also 
in human beings many times ; and anyone conversant with the 
subject can convince himself by combined cultural and inocula- 
tion experiments that certain microbes cause certain diseases. 
The objection that the microorganisms are not the cause but 
the accompaniment or product of the disease can easily be proved 
worthless. Of course there are microbes in the body which have 
nothing to do with disease, merely surface inhabitants of the 
integument and mucous membranes, able to penetrate into the 



56 Causes of Disease. 

blood and internal organs only after death of the animal (mostly 
putrefactive organisms). 

Those parts of the human or animal body which are freely 
accessible are exposed to the entrance of bacteria as of anything 
else from the exterior. Many of these microorganisms find fa- 
vorable conditions for existence in the surface of the skin and 
mucous membranes, live and multiply there without doing harm, 
finding their nutrition in the secretions and refuse of such lo- 
calities. They come from the air where they exist in the dust, 
from food and drink, and, in fact, from any objects in which 
they exist and with which contact is had. In our alimentary 
tracts there are always millions of bacteria* and other fungi, in 
the stomachs of ruminants countless infusoria, all of which par- 
take of the nutrient fluid and aid by certain secretions of their 
own in the digestion of the food, but have no pathogenic action; 
they are our table guests (commensualists) and stand in a re- 
lation of symbiosis to us (living together for mutual profit). 
As long as these conditions are maintained and as long as they 
obtain their nutrition merely from the dead material they may 
be considered as harmless saprophytes (aawpos, decayed; <t>vrov, 
vegetable growth). Their harmlessness is explicable by the fact 
that these microorganisms are not in any way fitted for attack- 
ing the living substance of the animal body, and their metabolism 
gives rise to no products which might be toxic to the cells and 
tissues of the animal ; or whatever toxines there may be are 
quickly neutralized by the body secretions. Besides, their increase 
is held in check by the various adjustment powers of the body. 
The protective epithelium of the skin and mucous membranes 
prevents their penetration into the tissues ; they are expelled 
from the air passages by the activity of the cilia of the lining 
epithelium and from time to time by the expectoration of mucus; 
many are retarded in their growth by the acidity of the gastric 
juice and by the intestinal secretions, as well as by the bile ; 
large numbers are expelled with the excrement from the in- 
testines ; many dry up upon the surface of the body. Moreover, 
the various organs and cells, as the liver and phagocytes and the 
blood particularly, contain substances of antitoxic and microbici- 

*A stained smear preparation, should be made from the surface of the gums, 
tongue or throat of a convenient cadaver as proof of the interesting flora existing 
there and as evidence of the wandering corpuscles in our cellular constitution. Vid. 
for fuller consideration Kitt, Bakterienkunde f. Tierdrzte, IV. Aufl. Wien, 1903. 



Infectious Agents. 57 

dal power; and even though they have gained access into the 
blood, bacteria may by these agencies be rendered harmless. 

There must, therefore, be special conditions afforded before 
a microorganism can become the actual cause of infection. In' 
the first place the microbe must possess peculiar toxic powers. 
All microbes carry on metabolic processes and elaborate a va- 
riety of chemical substances in the medium in which they exist. 
If among these products there be any which are harmful to ani- 
mal tissue, the possibility of toxic action exists. Since Brieger 
called attention to these substances and indicated their relation to 
disease occurrence, many of these microbic poisons have been 
proved to exist by various investigators and the process of infec- 
tion is recognized as invariably connnected with intoxication. 

In one class of microorganisms, the bacteria, poisons have 
been demonstrated which are apparently free, soluble secretory 
products of the bacterial cells, and which exhibit strong simi- 
larity to ferments. These poisons are as yet not well defined 
from a chemical standpoint; they are quickly rendered inert by 
being heated (to 50 to 8o° C.) and are peculiar in that they 
do not manifest their activity at once, but require a certain 
period of incubation. They are, moreover, especially peculiar 
in their specificity and in the fact that when introduced into a 
susceptible animal there is invariably a specific antitoxine gener- 
ated. They are, therefore, not a homogeneous product of all 
bacteria, but differ among themselves from their origin and the 
particular kind of microbe, each as a special product of a special 
process. These poisons are collectively called toxines. 

According to Ehrlich's theory, a toxine is a poison which possesses 
two specific groups of atoms, one of which, the haptophore, anchors the 
toxic molecule to the cellular protoplasm for which it has affinity ; the 
second, or toxophore group, doing the harm, supplying the real poisonous 
agent. v The toxines act then because they enter into chemical combination 
with the cells. (Vide Chapter on immunity, pp. 18 and 22.) 

The proof that a microorganism secretes a toxine and through 
it produces disease of the animal body is shown by the following: 
Many bacteria can be grown artificially upon nutritive culture 
media, as bouillon. If they secrete soluble toxines these will 
accumulate in the medium. If such a culture be passed through 
a filter impervious to bacteria, as a porcelain filter, the bacteria 
will be retained by the filter and the bouillon will pass through 
clear and quite free from bacteria. If there follow the injection 



58 Causes of Disease. 

of such a germ-free filtrate (into a suitable animal) evidence of 
toxic action, especially a specific one, then we must be dealing 
with a dissolved toxine yielded by the bacteria. The best and 
simplest example of this is afforded by cultures of tetanus bacilli, 
the filtrate from which produces typical and characteristic te- 
tanus symptoms, the dry residue from the evaporation of the 
filtrate acting in the same manner. 

A second proof that the immediate agent of bacteria is their 
soluble toxine may be had by artificially removing the latter from 
the germs. If water be allowed to run for several hours through 
the residue of bacteria upon the filter they will be washed free 
of the toxines and can be inoculated in enormous amounts, by 
the millions, without giving rise to apparent harm (the inert 
bacterial cells being quickly destroyed by phagocytosis in the ani- 
malbody). Yet if these harmless bacteria be returned to a nutri- 
tive medium where they can again multiply, they produce poison 
anew, this collecting in the substance of the bacteria and in the 
fluid in such quantities that inoculation of even the smallest 
quantity, a very few of the bacteria, will produce fatal effects. 

The virulence of toxines is remarkable ; a hundred-thousandth 
of a cubic centimeter of the filtrate of a tetanus culture is sum- 
cent to kill small animals, and a ten-thousandth of a milligram 
of the dried substance will do the same ; less than one milligram 
would cause tetanus convulsions in a human being. Such facts 
prove that some bacteria are provided with toxic agencies of 
frightfully dangerous power and explain why, when such causes 
of disease gain entrance into the human or animal body, they 
prove victorious in their conflict with the animal cells. 

Toxins do not act uniformly upon all animals. Intoxication oc- 
curs only when they enter into chemical combination, only in 
bodies whose cells possess substances (receptors) capable of union 
and having chemical affinity for the toxine. In bodies in which 
such receptors do not exist the toxine behaves as an indifferent 
substance. This explains why certain animals show a natural 
immunity against certain toxines and why the bacteria producing 
the latter are harmless to these animals, as chickens are insus- 
ceptible to tetanus toxine. 

There are some germs which produce no toxine separable by 
filtration as a secretion, but whose toxicity is occasioned by sub- 
stances enclosed in the body of the microbe and fixed there 
( endotoxines). Some of these substances are of albuminous na- 



Infectious Agents. 59 

ture {toxalbumen, mycoprotein, bacterial protein). They vary 
in their composition and modes of operation, some being peculiar 
to certain kinds of bacteria, others common to several forms. In 
general they act like albumens foreign to the animal, causing in- 
flammatory changes, necrosis of cells and tissues and exciting fe- 
brile reactions. The dead bodies of the bacteria act in the same 
way to some degree, their toxic substances being freed only by 
the death and maceration of the microorganisms. 

A number of bacteria produce pathological changes also by 
elaboration of' acids and gas-forming substances, as sulphuretted 
hydrogen. 

In addition to their chemical action it should be said that 
mechanical disturbances may be occasioned by bacteria which, in 
their multiplication, produce masses, perhaps for example ob- 
structing the blood vessels. 

The sum total of the pathogenic properties of a microbe is 
spoken of as its virulence. According to the quality of toxine 
produced and the energy of growth of the microbe in the animal 
body, there may be recognized gradations and differences of in- 
tensity of virulence of the various genera, species, strains and 
individual microbes ; their power of disease production corres- 
sponding with the same factors. Just as in artificial culture 
in a number of nutrient media a bacterium will either elabo- 
rate much toxine and grow rapidly or will produce but little 
toxine and grow slowly, according to the composition, reaction 
and temperature of the medium ; so in different kinds of animals 
there is a variation in capability of growth and toxine production 
of a given microbe. In adaptation to the conditions of nutrition 
afforded in a given body microorganisms may in greater or less 
measure lose the power of growth exhibited in some other body, 
may be altered in their pathogenic power ; this is spoken of as 
change of virulence by transmission. Such change may manifest 
itself either as an attenuation or as an intensification of virulence. 
The oldest known example of attenuation by transmission is seen 
in the change of virulence of the germ of smallpox ; variola, which 
in man is severe and marked by pock eruption all over the body, 
produces in the cow merely a local and mild eruption. In the 
cow, moreover, even in the first generation, it is permanently so 
attenuated that after reinoculation in man it gives rise to only 
a benign local eruption (not a general one). Wide differences 
of virulence exist' between the different strains [growths (A the 



60 Causes of Disease. 

same organism from different sources] of the tubercle 
bacillus ; those obtained by culture from the human body have 
become almost non-virulent for cattle by their adaptation to man, 
although some strains are readily transmissible. Avian tubercle 
bacilli are innocuous for mammals (except rabbits) and conversely 
it is difficult to infect chickens with human tuberculosis. How- 
ever, Nocard succeeded, by placing human tubercle bacilli, inclosed 
in collodion sacks containing bouillon, in the peritoneal cavity of 
chickens, in so adapting their growth to the avian body that there- 
after (in later generations of the culture) they became pathogenic 
for birds as well as men. 

In part, at least, the variability in the virulence of microbes 
of the same species must be recognized as a reason for the 
occurrence of either a comparatively mild or a severe course of 
an infectious disease (formerly called genius epizooticus) as well 
as for its self-limited termination. For example, mouth and foot 
disease in some of the epidemics which sweeps the country runs 
an unusually severe course with high mortality, although under 
ordinary circumstances it is not a fatal disease, recovery taking 
place in the course of two weeks. The investigations of Loeffler 
have shown that the virus of this plague, if inoculated from 
cow to cow, gradually loses its pathogenic powers, whereas if 
alternately transmitted from cow to swine in a long series the 
virulence is maintained or even increased. It is interesting, too, 
that pathogenic organisms may be influenced in artificial cul- 
ture outside the body so that their virulence may be either in- 
creased or diminished {change of virulence by artificial culture 
methods). Toussaint and Pasteur, who were the first to estab- 
lish this possibility, have demonstrated that anthrax bacilli, 
promptly fatal to cattle, sheep, rabbits and mice, may be so 
attenuated in virulence by artificial culture in bouillon at a tem- 
perature of 42 C. that they produce fatal effects only in mice. 
Similar facts have since been established in connection with a 
number of microorganisms capable of artificial cultivation, culmi- 
nating in efficient methods of prophylactic inoculation (Pasteur). 

This is easily understood when we realize that the attenuated 
germs give rise to but a mild attack of the infection when inocu- 
lated, which, however, leaves behind an immunity to the disease. 
On the other hand, an intensification of the virulence, even of 
microorganisms ordinarily without pathogenic influence, has been 
obtained by other cultural methods, as in nutrient media rich in 



Infectious Agents. 61 

albumens and in the absence of oxygen (Wiener, Hueppe). From 
such considerations it may easily be appreciated that virulence is 
a very variable property.* 

It is also essential for the development of an infectious dis- 
ease that the infectious agent should be afforded a suitable path 
of entrance or atrium to the tissues. Mere contact with a micro- 
organism does not necessarily result in disease ; there are often 
pathogenic microbes upon the surface of the skin and mucous 
membranes, the host in no wise suffering in consequence. The 
virulent germs of tetanus and of spreading gangrene are very fre- 
quently present in the intestinal canal of herbivora and omnivora, 
but without inducing pathological results as long as the mucous 
membrane is intact, their toxines being neutralized and destroyed 
by the digestive juices. So, too, pyogenic and putrefactive micro- 
organisms are found in large numbers in the intestinal contents 
and externally upon the skin in healthy human beings and animals, 
becoming pathogenic only in case of introduction into the lymph 
and blood through some tissue lesion. 

The ordinary places through which microorganisms gain ac- 
cess to the tissues are the external skin with its gland pores, the 
digestive and respiratory tracts, the conjunctival mucous sur- 
faces and the uro-genital passages. The protective epithelium of 
the skin and mucous membranes interferes with the penetration 
of most bacteria into the tissues and with their toxic action, partly 
because of the impenetrable barrier afforded (the horny epithelial 
layer), partly because the secretions of normal mucous membranes 
may wash off and destroy the microorganisms and dilute 
their toxines to such an extent that they are rendered inert or 
neutralized. This protective means is not an absolute one against 
some of the bacteria. Some may directly or by growth-extension 
penetrate the unaltered skin or mucous membranes ; or, having 
gained entrance to sebaceous and sweat glands, especially the 
glandular ducts or lymph follicles (which are open upon the 
surface as in the pharynx and intestine), may be carried into the 
deeper structures by leucocytes (glandular or follicular infec- 
tion). Many microbes are provided with means of motility (flag- 
ella) and are thus able to penetrate into canals, or from a surface 
may find their way into slight depressions or inappreciable defects 
in the epithelium, where, after local increase, their toxic metabolic 

*See further Kitt, Bakterienkunde fur Ticrarztc, M. Perle, publisher, Wien, 
1903, 4th edition. 



62 Causes of Disease. 

products naturally come to reach such a degree of accumulation 
(concentration) that further tissue change is caused and opportu- 
nity thus afforded for further penetration by the germs. In this 
manner rats may be infected by plague by merely dropping upon 
the unaltered conjunctiva the plague bacteria; and the trypansome 
of dourine (horse) invades the body by its own motile power 
through the mucous membrane ; various bacteria, if they can gain 
entrance into a duct in the nipple of the mammary glands, may 
multiply luxuriantly in the milk and give origin to intense sup- 
purative inflammation. 

Microbes gain access to the digestive tract along with food 
and drink or may be swallowed after being inhaled with dust. 
The special point of infection (so-called intestinal or food in- 
fection) in this case is usually the lymph glands of the mouth 
and pharynx, or of the intestine ; by the same route it is possible 
that the toxic products of microorganisms, themselves confined to 
the interior of the intestinal canal, may be absorbed through the 
blood and lymph channels. 

Microbes gain access to the respiratory tract by inhalation 
(inhalation infection) with dried dust particles or in the fine dis- 
charge coughed up by diseased animals and subsequently dried. 
They are in this case in part retained on the nasal mucous mem- 
brane, in part adhere to the pharyngeal surfaces and may thence 
pass into the lymph follicles and extend by route of the lymph- 
atics or be swallowed (giving rise indirectly to an alimentary 
infection), or they may be carried by the currents of air into the 
lungs directly. 

Infection of the urogenital mucous membrane usually takes 
place by transmission of the germs from one to another indi- 
vidual in the course of sexual congress (coital infection). 

A most favorable opportunity for infection is afforded by 
wounds of the skin or mucous membrane (wound infection), 
affording access to the microbes into the lymph spaces and chan- 
nels of the connective tissue, to the subcutaneous and sub- 
mucous structures, favoring penetration into the peritoneal cavity 
and eventually into the blood. The wounds may be so small as 
to be inappreciable to the unaided eye, as some tiny abrasion of 
the epithelium ; or it may be that before the disease actually 
appears there may intervene a considerable period of time, the 
wound perhaps long healed, so that the point of entrance is en- 
tirely lost (cryptogenetic infection; kpvtttcip, to conceal). This 



Infectious Agents. 63 

latter is often the case when we are dealing- with a follicular in- 
fection. The various pathogenic microbes do not possess uni- 
form powers of disease production, of multiplication and dissemi- 
nation, granted that they gain entrance by one or other of the 
points suggested. Some give rise to infection, no matter from 
what point they are introduced ; that is, they are capable of 
activity from various atria (tubercle bacilli). Others require 
introduction in certain situations in order that they may show 
pathogenic effects, a fixed point of access. For example, the te- 
tanus bacillus, as already indicated, can only be actively patho- 
genic from wounds ; the germs of vaginal catarrh and epidemic 
abortion naturally (partly effective also in case of intra- 
vascular inoculations) involve only the genital mucous mem- 
branes ; the bacteria of mastitis invade the lactiferous ducts 
only; the bacteria of calf diarrhoea confine their activity to 
the stomach and intestines. These peculiarities probably depend 
upon the presence at the appropriate points of entrance of es- 
pecially favorable conditions for multiplication of the germs, 
other parts presenting certain interfering conditions. 

Many germs require some special underlying condition in 
order that they may live and multiply. For example, the piro- 
plasmata must get into the blood, because they can only obtain 
their sustenance under the conditions afforded by the living blood 
and die out in the body fluids. Other organisms, as the colon 
bacillus and vibrio of Metschnikoff, thrive best in the chyme and 
intestinal mucous membrane. 

Doubtless the condition of the cells and juices of the body 
plays some part in the question of development of the infection. 
The biological and biochemical differences in cells and fluids, 
designated as tissue predisposition and tissue immunity, are indi- 
cated by the fact that a given species of animal is by nature com- 
pletely resistant to a certain microbe and its toxine, surely lethal 
for some other species, and by the varying rates with which dif- 
ferent tissues are involved, as where practically only one of the 
tissues offers resistance to the growth of the microbes (as the 
resistance of muscles to tuberculosis) or where but a single tissue 
is involved. Hence the question of development of an infectious 
disease depends not only upon the existence of a given essentially 
virulent microbe, but also upon the defensive powers of the body, 
upon the antitoxic and microbicidal properties of its organs and 



64 Causes of Disease. 

upon the mechanical obstruction to the penetration of the germ 
into the tissues (vide pp. 18, 21). 

The interval between the entrance of the microbes into the 
subject and the manifestation of appreciable symptoms is 
spoken of as the period of incubation. The length of this stage 
depends upon the vital peculiarities, the virulence and number of 
the microorganisms, and upon the site of the infection and the 
predisposing factors in the animal affected. If the microbes 
are capable of rapid multiplication and of generating large 
amounts of toxic material (as the bacteria of chicken-septicaemia, 
which rapidly increase in the circulating blood, or the colon bac- 
teria of mastitis which thrive luxuriantly in the milk of the 
udder) the period of incubation is usually of but a few hours' 
duration. Microorganisms of slow growth, as tubercle bacilli 
and actinomycetes, induce functional disturbances only after the 
structural changes which they bring about have attained a certain 
grade of development, and of necessity extend their period of 
incubation over weeks and months. Before the symptoms are 
appreciable clinically extensive anatomical changes may in many 
cases have developed, whence it follows that a disease may be 
latent or occult in its period of incubation, although if the animal 
be slaughtered it is clearly seen to have been present for some 
time. For example, in the case of pleuro-pneumonia in cattle there 
are often found characteristic appearances of the pulmonary in- 
flammation in animals which have been slaughtered when appar- 
ently quite healthy ; and in hogs affected with erysipelatous valvu- 
lar endocarditis of intense grade, the disease may be discovered 
only on slaughtering, the animals having shown in life no 
symptoms of a character to have suggested the existence of 
their disease. In rabies and tetanus, in which the virus causes 
symptoms only after it has become fixed in the cerebral nervous 
system [the toxine in case of the latter rather than the germ 
itself], the disease manifests itself the more rapidly the closer 
the point of infection to the brain; if the virus be inocu- 
lated directly into the brain the incubation lasts but a few days, 
while in case of ordinary subcutaneous inoculation it may be 
prolonged to weeks, the virus being at first retained in the lymph 
glands. Cases of infection of human beings by the bites of 
rabid dogs manifest rabies in 8-14 days where the wounds are in 
the face, but when the hands or feet have been bitten the period 
of incubation lasts usually one or two months, and sometimes the 



Infectious Agents. 65 

disease does not appear for a year. The influence exerted by 
the virulence, the amount of toxine and the particular infec- 
tious germ upon the period of infection may be appreciated after 
introduction of tetanus toxine into mice ; the symptoms of the 
disease, depending upon the dosage, appearing after varying inter- 
vals from 12 hours to 2 — 6 days. 

The dissemination and multiplication of pathogenic germs in 
the body exhibit a number of peculiarities. Some micro-organ- 
isms remain closely confined to the immediate vicinity of the 
point of infection, giving rise from this localized situation to toxic 
results in proportion to their own disintegration and to the ab- 
straction by the fluids of the body of their toxic substances. Thus 
they may cause lesions only in the neighboring tissues or induce 
intense general disturbance after absorption. The tetanus bacillus, 
for example, does not grow free in the body (except in the uter- 
ine cavity, where, under anaerobic conditions, the organism can 
accumulate in large quantities after having once been introduced) ; 
in the course of a day or two after inoculation it can no longer 
be found at the site of infection (wound), nor elsewhere in the 
body. It disappears because of its disintegration and through the 
agency of the phagocytes. Its toxine, however, is absorbed and 
causes the ganglion cells to undergo necrobiotic changes. Often 
bacteria, as the pyogenic organisms, increase by multiplication at 
the site of infection, but are prevented from further extension by 
the defensive properties of the body. 

For the most part the germs are distributed from the point of 
infection along the lymph channels, in part at least because the 
newly developed germs are produced about the borders of the focus, 
are swept away in the lymph plasma or are taken up by the leuco- 
cytes and carried elsewhere. The local focus (local infection) en- 
larges directly into the surrounding regions, (regional infection) ; 
and the microbes, conveyed by way of the lymph channels, are car- 
ried deep into the tissues to the lymph glands, from one site to an- 
other, from one lymph gland to another, until they finally reach 
the blood. They may also gain direct entrance into the capillaries, 
veins and arteries from the point of in feci ion (as in wounds or 
ulcers, or by direct extension by growth through the vessel walls) 
and be carried along with the blood current (embolic or hemato- 
genous infection). There thus are produced at a distance from 
the point of entrance or primary focus of infection new deposits 
of the infectious agents; and cither new local 1 of dise.i 



66 Causes of Disease. 

secondary metastatic foci of infection, are caused, or the micro- 
organisms are widely disseminated throughout the whole body 
(general infection, bactericumia) . As an illustration, streptococci of 
epidemic coryza in the horse gain access to the pharynx with the 
drinking water or with the inspired air; they here first give rise to 
a purulent catarrhal inflammation, penetrate by direct growth into 
the pharyngeal follicles, gradually make their way along the 
Eustachian tubes to the middle ear and here set up a similar puru- 
lent inflammation. Being carried away by the lymph current and 
by leucocytes, they give rise to abscess formation in the retro- 
pharyngeal lymph glands, and by going lower, in the cervical nodes ; 
and, too, they may be swallowed and infect the mesenteric lymph 
glands as they pass along the chyliferous tract. Passing from the 
lymph glands to finally reach the blood, they are disseminated by 
the latter generally throughout the body, and cause a variable num- 
ber of metastatic abscesses in such situations as the brain, lungs, 
liver and kidneys, eventually a septico-pysemia. In similar way 
infection of the umbilical vein in the new-born by pyogenic bacteria 
causes primarily a local abscess-formation at the umbilicus, fol- 
lowed by multiple venous-embolic abscesses in the liver, later in the 
lungs, the joints and elsewhere. 

It may happen that at the point of infection the local lesions 
are so slight as to be appreciable only by microscopic study, that 
the microbe passing from this point first lodges in the lymph 
glands or may perhaps even pass through several lymph-nodes 
without occasioning any disturbances, multiplying and manifesting 
its influences only after it has gained access to the blood and 
circulated in the body and become fixed in this or that position 
at a distance from the original site of entrance. The tubercle 
bacillus, for example, may be absorbed from the intestines with- 
out causing any alterations in them, but giving rise to caseation 
of the mesenteric lymph-nodes ; or these may be traversed by it, 
the germ gaining access to the blood, and perhaps first deposited 
in the bone-marrow, where it gives origin to the primary tubercu- 
lous focus. 

The physiological movements and changes of position of the 
intestines and muscles aid in great measure the spread and dis- 
tribution of the invading and multiplying microorganisms ; 
pyogenic microbes which have gained access to the peritoneal 
cavity are apt to be spread over the whole peritoneal sur- 
face by the peristaltic movement of the intestine, the resulting peri- 



Infections Agents. 6j 

tonitis as a consequence being generally a diffuse one. Tuber- 
cle bacilli having effected an entrance into the pleural or peri- 
cardial cavities multiply in the lymph and are actually rubbed 
into the whole serous surface by the movements of the heart and 
lungs. For this reason there usually occurs in these regions a 
disseminated, dense eruption of tubercles involving the whole 
pleura, pericardium and epicardium. So, too, currents in the 
secretory fluids on mucous surfaces are favorable to the dissemina- 
tion of microorganisms ; and the covering of these surfaces permits 
migration and generalization, especially of the motile forms. 
Tubercle bacilli may thus reach the larynx in the bronchial secre- 
tions from cavities in the lungs, and if retained may occasion 
laryngeal ulceration ; pyogenic bacteria from the pharynx may pass 
to the Eustachian tubes and middle ear in horses ; and in case of 
infection of the milk ducts of the nipple the different kinds of bac- 
teria in the milk and milk passages advance into the parenchyma 
of the udder and give rise to mastitis. 

The pathogenic action of bacteria is, as already indicated, for 
the most part a toxic process, but also in some degree a mechan- 
ical one; it is governed both by the properties and the quantity 
of the extremely varied metabolic products elaborated by the 
individual microbes, but is also dependent upon factors deter- 
mined by the place of infection and by the predisposition of the 
tissues. Local and general effects are distinguishable ; first by the 
fact that at the original point of infection and at metastatic locali- 
ties anatomical lesions are originated (inflammations, degenera- 
tions, necroses, proliferations, depending upon the nature of the 
microbe, both in the sense of a mere foreign body and of the pecu- 
liarity of its constituent materials) ; and, second, by the develop- 
ment of general metabolic disturbances, especially fever, from the 
generalization of the infectious agents and their products. In 
each case the phenomena are expressions of tissue reaction to the 
noxious foreign microbe undergoing multiplication from time to 
time in the system (v. chapters on fever, limiting inflammation). 
Each kind of pathogenic microorganism manifests a fixed mode 
of action, determined by its manner of multiplication in the tis- 
sues and the particular nature of its toxic product (specific 
action), and therefore produces a specific disease. In case of 
other causes of disease there is no uniformity of action, but, on 
the contrary, a variability ; or, better, it may be said that other 
or non-infectious diseases may occur in the same form from the 



68 Causes of Disease. 

effect of a variety of agencies. A nasal catarrh may be caused 
by the inhalation of dust, irritant gases, chemical fluids, the 
influence of cold upon the external surface of the body, or from 
infection; cold may produce in one subject painful peristalsis 
(colic), in another muscular rheumatism, in a third a coryza, a 
pneumonia, an intestinal catarrh. In infectious diseases the body 
generally reacts with uniformity in a definite manner ; the basic 
symptoms and lesions are invariably manifest, and it is possible 
to decide from the presence of certain signs of the disease that a 
definite type of infection exists. By specificity, therefore, we 
understand that each infectious disease is the result of fixed in- 
fectious agents and not of anything else. Anthrax is always 
caused by the anthrax bacillus, and never by any other microbe 
or noxious agency of any sort ; glanders is caused by the glanders 
bacillus ; smallpox by the smallpox contagium. There are, how- 
ever, some micro-organisms which, because of similarity of toxic 
properties and analogous modes of multiplication, give rise to the 
same anatomical tissue changes, so that clinically the same 
anatomical types of disease are produced by several kinds of 
germs (the groups of the pyogenic bacteria, the micro-organisms 
of septicaemia, of moist gangrene and of mastitis). Such in- 
fectious diseases are said to be polybacterial. 

Variations in the duration of infectious diseases, modifications 
and degrees of anatomical changes, are proportioned in the sever- 
ity of the infection to the grade of virulence of the microbes, 
and are dependent as well upon the place of entrance of the infec- 
tion and the predisposition of the tissues. Just as a corrosive 
substance, an acid, depending upon whether it comes in contact 
with animal tissue in concentrated or dilute form, produces either 
an eschar, tissue necrosis, inflammation or mere hyperemia, so a 
difference is appreciable in the action of microbes according as 
they are highly toxic or more or less attenuated. The importance 
of the factor exerted by the place of entrance of the infection is 
indicated by the studies of Arloing, Cornevin and Thomas upon 
the bacillus of symptomatic anthrax ("black leg") ; this micro- 
organism, if inoculated into the muscles and subcutaneously, kills 
animals after intense symptoms ; but if the inoculation be made 
into the trachea or intravenously there follows merely an abortive 
course, which, however, is succeeded by an immunity. Variations of 
susceptibility and resistive powers in different animal species and 
individuals to precisely the same infectious agent may cause 



Infectious Agents. 69 

marked variations in the clinical and anatomical picture of 
the same infectious disease. Thus a certain strain of glanders 
bacilli has been known to cause in a horse a chronic glanders 
lasting over several years, but in guinea-pigs and field mice a 
very acute type of the disease ; the bacillus of hog-erysipelas, pro- 
ducing in one hog an acute septicaemia, to cause in a second a 
slight urticaria, in a third a chronic cardiac valvular affection. 
The influence of tissue resistance upon the disease picture is 
especially apparent when inoculations of the organisms of chicken- 
cholera of high grade of virulence are made into rabbits previously 
treated by serum injection. Rabbits which have not been previ- 
ously subjected to serum injection succumb to hypodermic inocu- 
lation of but a small number of bacteria as early as from 12 to 24 
hours, dying of severe acute septicaemia ; those previously injected 
and then subjected to the same inoculation die only after 5 to 14 
days, and then show extensive purulent phlegmons, purulent and 
fibrinous pleurisy and pericarditis, or merely an anaemia as a re- 
sult of the prolonged infection. 

Recovery from an infectious disease usually leaves thereafter 
a certain degree of immunity (v. active immunity, p. 27). 

Sometimes several kinds of pathogenic organisms gain en- 
trance at the same time through one point of infection, the result- 
ant infection being thus a complicated one (mixed infection) ; or 
after the individual is attacked by one infection other types may 
invade (secondary mixed infection). The former condition is 
seen when the infective matter from the beginning contained sev- 
eral varieties of pathogenic germs, as where a wound is contami- 
nated with earth containing both spores of tetanus bacilli and pus 
bacteria, or where a cow's nipple is soiled with filth and dung 
m which there are streptococci and colon bacilli. So, too, micro- 
organisms which have existed indefinitely upon the surface of 
some mucous membrane may, if occasion presents, penetrate into 
the tissues along with some other type of infection and combine with 
the latter in producing pathogenic effects ; thus, should there be pro- 
duced by some foreign body an injury to the tongue or pharynx 
of the cow, the various putrefactive organisms living as sapro- 
phytes in the mouth may occasion with pyogenic bacteria a mixed 
infection. The second form of mixed infection, the successive 
invasion of a second or third pathogenic genu, may be noted 
where local changes from a primary infection bring about condi- 
tions which facilitate the access and growth of other microbes; as 



jo Causes of Disease. 

when ulceration has occurred in the primary infection and the 
protective epithelium has been lost, or when in the course of a 
disease the bactericidal substances normally present in the fluids 
of the body have been exhausted and the resistance of the tissues 
reduced in consequence. Not infrequently such mixed infection is 
to be seen in hog-cholera, the micro-organisms of which cause 
necrotic and coagulative destructive changes in the intestinal 
mucous membrane and general wasting; there is thus prepared so 
suitable a culture medium for the sputum bacteria and necrosing 
bacilli present in the pharyngeal mucus and in the intestinal con- 
tents that these readily penetrate into the tissues and materially 
contribute to intensify the disease and hasten a fatal termination. 
Admixture with or contamination (association) of an infection by 
one or more other types of pathogenic microbes, each with its 
special properties, and the combined action of all, as a rule causes a 
severe course of the infectious disease and occasions unusual 
pathological processes {complications) . 

The mere presence and microscopic recognition of several types of 
microbes in any focus of disease or in the tissues of the cadaver by no 
means warrant, without other knowledge, the assumption that there has 
existed a mixed infection ; after the death of the animal great numbers 
of saprophytic organisms living on the surface of the mucous membranes 
wander into the organs, and necrotic or ulcerating foci in the lungs, intestine 
or skin are apt to harbor the same sort of organisms from the air or food 
(so-called symbiotic bacteria). The association of such essentially non- 
pathogenic germs, or, too, of pathogenic microbes with another pathogenic 
variety, may (as especially pointed by Leclainche-Vallee in studies on 
symptomatic anthrax) determine actual infection ; for example, a symbiotic 
bacterium may prevent phagocytosis by a negative chemotactic power and 
thus produce conditions favoring the increase of the other infecting agent. 
This should not be interpreted as meaning that a given microorganism 
cannot alone cause its special disease, and that only when in association 
with other microbes can produce its effect ; it merely applies to special 
conditions in which the specific infectious agent is attenuated or is- situated 
in an unsuitable point for infection. All known pathogenic microorganisms 
are individually capable of giving origin to their peculiar infections, and 
each is the specific bearer of such infection. 

Those micro-organisms regarded as pathogenic may be classed 
in two groups : In the first group are microbes usually living in 
the external world, but inducing disease in the animal body if by 
accident they gain access to it (ectogenous infectious agents, 
facultative parasitic microbes). The diseases arising from this 
group affect individual animals here and there, or may attack a 



Infectious Agents. Jl 

number, provided there be opportunity of convection from their 
habitat in the soil to the animal body with water, food, etc. They 
are essentially of telluric origin, and it is customary to speak of 
spontaneous disease or miasmatic (t6 fxiaa/xa, from /uaivw, to con- 
taminate) origin in this connection. In the second group are 
included microorganisms which, being exclusively adapted to the 
animal body from an indefinite period, live and thrive in it as 
their habitat (entogenous infectious agents, obligate parasitic 
microbes). Diseases occasioned by these do not appear as spon- 
taneous infections, but occur only when a human being or animal 
comes in contact with a previously infected individual or with 
desquamated or excretory material from such an individual in 
such manner that the infectious agent can pass to the former. 
Such instances are spoken of as contagious infectious diseases. 
[Among many there is to-day a strong tendency to deny the 
existence of pure miasmatic infections, and thus to regard the 
terms contagious and infectious as synonymous, such persons hold- 
ing that the so-called miasmatic diseases are caused by organisms 
which are essentially facultative parasites, and in more or less 
direct manner have come from previously diseased individuals. 
The difference of view is by no means a vital one, and the 
author's recognition of their immediate derivation from a source 
other than a previously diseased individual is correct. In the 
sense that these facultative parasitic microbes once affecting an 
individual may be further transmitted, his division, however, be- 
comes unnecessary, since in this manner all infectious diseases are 
contagious.] 

A certain number of infectious maladies may be acquired in 
both ways; originating primarily from the soil, the microorgan- 
isms multiply in the animal body and then are transmitted from 
the diseased to other individuals (c out agio -miasmatic diseases). 

The fact that some microorganisms thrive only in the animal 
body and die when in the external world is a phenomenon of 
adaptation. It may be assumed that all these obligate parasitic 
germs originally lived a free saprophytic life in nature, but having 
accidentally gained access to an animal body thrived therein and 
by rapid succession of generations usual to such low organisms 
acquired a special adaptation for the conditions thus afforded and 
lost their faculty of propagation outside. 

Changes in nutritional conditions are likely to cause changes 
in their metabolism, and the influence which invading microbes have 



~2 Causes of Disease. 

upon the tissues of the body depends in part upon their metabolic 
activity and metabolic products. From investigations of Wiener 
it has been shown conclusively that a type of bacteria common to 
the human intestine and regarded as entirely harmless in this 
situation and in the excreta, can by special nutritive influence be 
so transformed as to acquire highly toxic properties (the so-called 
colon bacilli, living as saprophytes in the colon). If fed ordina- 
rily to rats they give rise as a rule to no disturbances whatever, 
but if the colon bacilli have been cultivated for a few days under 
anaerobic conditions on a medium specially rich in albumen (eggs) 
they acquire an intense virulence, and if fed to rats produce a 
severe and almost invariably fatal enteritis. Although such 
transformation of a non-toxic saprophyte into a toxic pathogen 
cannot off-hand be accomplished with other micro-organisms, this 
isolated fact proves that it is possible for infections of a character 
new and unknown to us to arise from time to time ; and as a 
matter of fact spontaneous infectious diseases do now and again 
appear which have not been previously observed and which are 
to be regarded as rarities. It is a pure accident when the special 
germs are brought into contact with the human and animal body ; 
and it is further conditional upon special circumstances of nutri- 
tion whether the microbe possess virulent properties, as in case 
of the meat intoxications caused by various microorganisms, 
sausage poisoning, diarrhoea and vomiting and wound infections. 
Some infectious diseases are of very frequent occurrence because 
the agent is widely disseminated in nature or because opportunities 
for transmission to the animal body are often afforded. For in- 
stance, the tetanus bacillus exists in the soil in many localities, 
and wounds are often contaminated by dirt, the opportunity for 
tetanus infection being correspondingly common. Such wide- 
spread microorganisms and their infectious diseases are spoken 
of as ubiquitous. As the alpine rose and reindeer moss, palms 
and cacti flourish only within certain geographical limits, and as 
poisonous snakes and the different kinds of insects have their 
habitats only in certain parts of the earth ; so certain microbes 
occur only in certain lands, where alone, too, the corresponding 
infectious diseases arise as spontaneous affections. Such districts 
are foci in which annually a certain number of cases are likely 
to occur, and it is said that the disease is established in such 
places (indigenous, endemic). Truly contagious diseases may 
also be endemic, provided in a certain district (irrespective of soil 



Infectious Agents. 73 

conditions) there are always a number of animals suffering from 
the special infectious disease, so that others from these may in 
turn acquire the affection. When an infectious disease occurs in 
isolated cases here and there it is spoken of as a sporadic disease ; 
if many or great numbers of individuals are affected, it is spoken 
of as a plague, an epizootic {epidemic) ; if it extend over large 
areas, and if not merely one species, but many, are affected, it is 
called a panzootic {pandemic^. Animal diseases transmissible to 
man may be spoken of as androzoonoses. 

The separation of spontaneous from contagious infections, the 
recognition whether a microbe is miasmatic or purely contagious, 
is of importance in dealing with epidemic diseases ; the purely 
contagious diseases can be eradicated by measures protecting the 
well from the diseased animals and their excrementitious matters. 
This has been demonstrated in the extirpation of cattle plague, 
pleuro-pneumonia and hydrophobia from districts in which for- 
merly they were rife. 

SUMMARY OF THE MOST IMPORTANT INFECTIOUS 
DISEASES AND THEIR AGENTS.* 

I. Bacteriaemias, Septicaemias. 

Bacillus avisepticus (Bad. aviscpticum s. avicidum) , septicaemia 
of birds and rabbits (chicken cholera).' 

Bac. pleurisepticus, sporadic and epidemic septicaemia of all 
domestic animals {bac. bovisepticus, suisepticus) , deer and cattle 
plagues, pasteurellosis bovis, 

Bac. anthracis, anthrax of domestic animals and man. 

Bac. ccdematis maligni, spreading gangrene of domestic ani- 
mals and man. 

Bac. sarcophysematos bovis, symptomatic anthrax of cattle. 

Bac. gastromycosis oris, bradsot of sheep. [ Bradsot is a dis- 
ease of sheep in northern Europe, by many regarded as a form 
of symptomatic anthrax.] 

Bac. pestis tarandi, reindeer plague. 

Bac. rhusiopathicu suis, swine erysipelas. 

Bac. suipcstifcr, hog cholera. 

Bac. pestis bubouiccc, human bubonic plague, transmissible to 
swine and rats. 



♦For detailed description and technique of Investigations, v. Kltt, BofcteHen- 
kunde f. Tierarzte, IV. Anil., Wlen, 1903. 



74 Causes of Disease. 

II. Toxic Infections. 

Bacillus tetany tetanus in all animals and man. 
Bac. botulinus, sausage poisoning in man. 
Bac. enteritidis, meat poisoning in man. 
Bac. dysenteries litulorum, diarrhoea in calves. 
Vibrio Metschnikovi, vibrio cholera of chickens [microspira 
Metschnikovi, irregular] . 

III. Inflammatory and Pyogenic Organisms. 

Staphylococcus pyogenes aureus (albus, f.ai'us, citreus), sup- 
puration of wounds, furunculosis. 

Streptococcus plilogogenes sive pyogenes (various forms), 
suppuration of wounds. 

Micrococcus tetragenus, umbilical suppuration in calves. 

Bacillus mallei, glanders in horses and man. 

Bac. lymphangitidis ulcerosa:, lymphangitis in horses. 

Saccharoniyccs farciminosus. iurunculosis in horses. 

Streptothrix farcini bovis, furunculosis in cattle [Xocard's 
pseudotuberculous nodules in the skin and viscera of cattle] . 

Streptococcus equi, contagious coryza of the horse. 

Bacillus acneos equi, contagious pustular dermatitis of horse. 

Bacterium phlegmasia uberis (a number of varieties), mastitis 
in the cow. 

Streptococcus mastitidis (a number of varieties), mastitis in 
cow. 

Micrococcus mastitidis gangrenosa ovis, mastitis of sheep. 

Bacillus pyclouepliritidis bozis, nephritis of cow. 

Bac. pyocyaueus, purulent inflammations. 

Bac. coli communis (a number of varieties), various forms of 
cellulitis, mastitis, nephritis and enteritis. 

Botryomyces ascoformans, suppuration and granuloma forma- 
tion in horse. 

Cladothrix canis, various suppurations in the dog. 

i 

IV. Diphtheritic Necroses. 

Bacillus necroplwrus, traumatic necrosis, multiple coagulation 
necrosis of mucous membranes, liver and lungs in cow, horse and 
sheep. 

Bac. diphtheria; columbarum, pigeon diphtheria. 



Infectious Agents. 75 

Bac. diphtheric? avium, chicken diphtheria. 
Bac. diphtheria; hominis, diphtheria in man, exceptionally in 
cats and birds. 

V. Tuberculosis and Actinomycosis. 

Bacillus tuberculosis, tuberculosis of man and the lower ani- 
mals (varieties in birds and cold-blooded animals). 

Bac. bronchiolitidis vituli, cheesy pseudotuberculosis of the 
lungs in the cow. 

Bac. pseudotuberculosis ovis, in sheep. 

Actinomyces bovis, actinomycosis of cow (with varieties). 

Streptothrix caprce, pseudotuberculosis of the goat. 

VI. Specific Diseases of the Sexual Organs. 

Bacillus abortivus vaccarum, epidemic abortion of cows. 
Micrococcus abortivus equi, epidemic abortion of mares. 
Streptococcus vaginalis vaccarum, contagious vaginitis of cows. 
(Trypanosoma equiperdum s. Hagelose) , dourine in horse. 
[SpirOchceta pallida, syphilis in man?] 

VII. Pleuropneumonia. 

The infectious agent of contagious pleuropneumonia of the 
cow. 

VIII. Epidemic Diseases Caused by Ultramicroscopic Agents. 

Contagium of foot and mouth disease, in cattle, swine, sheep, 
and transmissible to man. 

Contagium of cattle plague. 

Contagium of smallpox in man, transmissible to cow, horse, 
rabbits. 

Contagium of sheep pox. 

Contagium of rabies of dog, transmissible to man and all 
mammals. 

Contagium of Lombardy chicken plague. 

IX. Diseases Due to Flagellata, Piroplasmata and Sporozoa. 

Trypanosoma Evansi, surra in domestic animals in India. 
" Brucci, nagana in African animals. 

" equiperdum, dourine in horse. 



j6 Causes of Disease. 

Trypanosoma Theileri, African cattle plague. 

" Gambiense, African sleeping sickness in man.] 

Plasmodium malaria: equorum, African equine malaria. 

[Plasmodium of human malaria — tertian, quartan and sestivo- 
autumnal types.] 

Piroplasma bigeminum, epidemic hemoglobinuria of cattle, 
deer and sheep. 

Piroplasma caninum, infectious jaundice of dog. 

Sarcosporidia major and minor, parasites of muscle and cel- 
lular tissue in swine, cattle, sheep, goats and horses. 

Coccidium oviforme, dysentery of cow, intestinal and biliary 
duct parasite of rabbit (also in man and dog). 

Diseases Due to Mould Fungi. 

Monilia e and id a, thrush in man and birds. 

Trichophyton tonsurans (numerous varieties), bald patches in 
cow, man and dog. 

Achorion Schbnleinii (numerous varieties), favus in man and 
lower animals. 

Dermatomyces gallinarum, scab of cock's comb. 

Aspergillus fumigatus, pulmonary mycosis in birds (excep- 
tionally in horse and cow). 

Animal Parasites. 

Food and conditions favorable to the existence of a variety 
of animals and plants are afforded by the human and animal 
bodies, both in the fluids and tissues, and, too, in the nutrient 
ingesta and in the excretory and waste matter. When some organ- 
ism both acquires its nutrition and resides upon or in the body 
of another individual the condition is spoken of as parasitism 
(Trapd along with ; wos. food). A parasite, therefore, is a form 
of life which either transiently or permanently lives upon or 
in the body of another organism for the purpose of obtaining its 
nutrition therefrom (Braun, Heller). 

According to their origin from one or other of the two kingdoms in 
nature, they are separable into vegetable and animal parasites ; those which 
live on the surface of the body are spoken of as ectoparasites or external 
parasites (epiphytes, epizoa), those whose habitats are within the body 
as internal parasites or entoparasites (entophytes, entozoa). 

In the preceding chapters the discussion concerned infestment 



Animal Parasites. yy 

by microorganisms appreciable only with the aid of the micro- 
scope, the protophytes and protozoa, a condition spoken of as in- 
fection when leading to disease. Some of these microbes well 
merit the name parasites, since the animal body in which they 
exist is the source of their nutrition, but the toxic properties of 
the most of them are so conspicuous that we are likely to think 
of these not so much as parasites, but as comparable to poison- 
ous plants. 

A number of forms of worms and arthropoda (zooparasites) 
have gradually assumed the character of true parasites and actu- 
ally live and subsist upon the body structures. Occupation of the 
body, either externally or internally, spoken of as invasion 
(invadcre, to penetrate), is apt to give rise to a varied group of 
tissue alterations and disease processes (invasion diseases [infest- 
ment]). The individual in which such a zooparasite finds shelter is 
to be looked upon as the host of the parasite. Some infest the host 
only for a brief period as necessary for the acquirement of nutri- 
tion (transient or temporary parasites), or for the time essential 
for the completion of one or more stages of their development, 
among which groups respectively fleas and the larvae of gadflies are 
examples. Others are persistent and pass their entire existence as 
parasites (habitual or permanent parasites). The life of this 
latter type may be passed in some instances entirely in one host 
(mono.renous parasites; /j.6vos, one; £evos, host), or may be dis- 
tributed over several hosts (heteroxenous parasites) . 

Invasion of a host at times is merely the result of accident, 
in which case the parasite is usually taken in with food: in other 
instances this or that parasite may by its own independent move- 
ments gain entrance into the body. 

Parasitism may be referred to two underlying conditions, 
adaptability of the parasitic organism to the conditions of life af- 
forded by the body of the host and the biological variability of the 
former. Worms and arthropods which have assumed parasitic char- 
acteristics undoubtedly at one time lived independently in nature. Tt 
may be imagined that one of these low types of animals by acci- 
dent entered the body of sonic higher animal, and, finding condi- 
tions favorable for the acquirement of food, remained and multi- 
plied; that the offspring, now native to the body of the host, 
did not again seek a free state, but continued as parasites, being 
from birth accustomed to the altered environments. Such sup- 
position is justified by the fact that some parasite? still show nidi- 



78 Causes of Disease. 

merits of organs worthless to them in their present form of life, 
but which were evidently inherited from their free-living ancestors. 
For example, in linguatula tccnioides, a permanent parasite of the 
nasal fossae of the dog, there are rudimentary feet, probably 
better developed in the free-living predecessors, but stunted in these 
parasitic descendants from lack of use. In the same way may be 
explained the absence of wings in parasitic insects ; for example, 
sheep lice have probably developed through atrophy of their 
wings from disuse of these organs, for there are allied species of 
insects which are not parasitic and possess wings. On the other 
hand, gradual adaptation to life upon an animal host leads to the 
acquirement of new peculiarities on the part of the parasite, as a 
transformation of masticating mouth parts into piercing and 
suctorial organs and the development of special types of organs 
for attachment and holding. Such adaptations and transforma- 
tions of structure are of such common occurrence throughout na- 
ture, even in case of the human body (formation of a horny sole 
on the back of the foot, originally soft, in cases where from some 
disease the dorsum of the foot is turned down and walked on ; 
transformation of the toes into prehensile organs by practice), 
that, as it is true in the higher animals, there is no wonder that 
it should occur in these lower invertebrates whose tissues are 
much more capable of such adaptive growth. The newly ac- 
quired characteristics become fixed in the succeeding generations 
because of heredity and because of uniformity in the vital condi- 
tions about them ; some species which have gradually assumed 
parasitic nature are finally restricted entirely to a parasitic life 
and are unable to live in the external world ; others pass only a 
part of their lives, a definite developmental stage, as parasites, and 
for the rest of their time live independently. There are certain 
filarial worms which ordinarily live in moist earth, but which now 
and again, as necessity arises, become parasitic. As the moisture 
disappears these worm retreat into depressions where the moisture 
is longest retained, but should a snail or earth-worm happen in 
their way they pick out the cavities of these animals and creep 
into them. In protracted drouths they are parasitic for a corre- 
spondingly long period, and it has been observed that in such 
parasitic existence they attain unusual size and produce a larger 
number of ova than their free-living fellows (Braun, Heller). It 
may be that the young brood continue in the snail and become 
completely transformed into parasites, but the original ones, when 



Animal Parasites. 79 

wet weather returns, abandon their parasitic hiding places. L. 
Oerley has succeeded in artificially causing a free species of worm 
(rhabditis pellio) to live temporarily as parasites by introducing 
them into the vaginae of mice, where they continued to live and 
multiply, although when placed in the digestive canal they died or 
were expelled. Larvae of flies often resort to parasitism as oppor- 
tunity is afforded ; meat flies and other insects which are ordinar- 
ily saprophagous often oviposit upon some animal in wounds or 
ulcers and the resultant maggots obtain their nutrition in the 
same location as parasites, although succeeding generations con- 
tinue as usual under other conditions of existence. It may be 
supposed that frequently such assumptions of a parasitic existence 
are brought about by the force of circumstances and end with 
the death of the organism if it be incapable of adaptation, even if it 
should succeed in getting nourishment from the body of the ani- 
mal host. Only in case the intruding worm (or other form of 
life) can successfully withstand the mechanical and chemical influ- 
ences which oppose it, only in case it obtains a habitat where it is 
possible for it to live, is it likely to be changed into a parasite. 

Some worms may be parasitic in different animal species ; 
trichinella is parasitic in man, hog, rat, mouse, cat, fox, polecat 
and bear, and may be artificially induced to infest the dog, rabbit, 
guinea-pig, sheep, horse and other mammals. In the same way the 
liver fluke is found in a number of species. Other parasites, on 
the contrary, occur in only one fixed species. For example, tenia 
solium and tcenia saginata are found only in the human intestine ; 
crassicolis only in the cat ; in the intestine of another species they 
die and it is impossible or only an exceptional case that they 
should persist. Such exceptions, however, do occur naturally as 
well as in artificial attempts to infest. For example, bothrioce- 
phalus latns, whose normal host is man, is occasionally found in 
the intestine of the dog; ech'ynorhynchus gigas, a parasite of the 
intestine of the hog, is in rare instances met in man. Such cases 
are to be explained by exceptional opportunities for transmission. 

The influence of parasites upon the host varies much accord- 
ing to their habits and situation. Tn many instances the presence 
of a parasite occasions no noticeable disturbances ; dogs may have 
dozens of tapeworms in them without showing any evidence of 
sickness, although in other cases even a small number of the same 
tapeworms cause digestive disturbances. At one time it was sup- 
posed that some parasites were of use to the host, as the larva? 



80 Causes of Disease. 

of one of the gastric flies (gastrophilus salutaris — so named from 
this idea) ; it was thought that their presence in the stomach and 
small intestine of the horse promoted the secretion of gastric 
juice ; or it was believed that some parasites consumed superfluous 
mucus. Although it is reasonable to suppose that some parasites 
obtain their nutriment from the waste matter (as is true of the 
infusoria and bacteria always present in the stomach in rumi- 
nants) and take part in the breaking up the intestinal contents, 
yet it is not to be concluded that the parasitic worms and arthro- 
pods have any value whatever to their host. On the contrary, the 
animal host, if rid of them, will thrive equally and better. All 
parasites exert from time to time some harmful influence, and 
some are death-bearing guests. 

In the first place, many parasites are harmful to their host and 
productive of disease by their wandering in the body and their 
movements. Undoubtedly the itching caused by the crawling para- 
sites inhabiting the skin-surface, and often giving the host no 
rest day or night, has some influence upon the health ; here may 
be mentioned the sheep-lice, itch-mites and the oxyurides inhabit- 
ing the rectum and causing continual tickling sensations, as per- 
fect torments which often give rise to emaciation (due to the in- 
crease of metabolism following the incessant restlessness from the 
itching). Other parasites make their way through the tissues by 
boring, and thus where any considerable number penetrate into 
the organs cause tissue destruction and occasion haemorrhages and 
inflammatory lesions (lesions produced by liver flukes, larval tape- 
worms and linguatulidae). They may give rise to a great variety 
of disturbances, just as any foreign bodies in a mechanical way, 
by compression of tissues, or by obstruction and narrowing of 
tubular passages, as sudden death by invading the brain, paralysis 
by pressure on the spinal cord, atrojphy of the liver by growth in 
its parenchyma, blindness by penetrating into the eye, rupture or 
thrombosis of the larger blood vessels, respiratory interference and 
suffocation by lodgment in the air passages and lungs, and intesti- 
nal obstruction. The parasites adhering to the intestinal mucous 
membrane by hooklets or suctorial apparatus often produce re- 
flexly marked irritative or perhaps nervous phenomena ; and, too, 
a toxic influence is to be ascribed to the metabolic products of a 
number of worms which may be reasonably thought to explain 
the occurrence of nervous changes and general loss of flesh (as in 



Animal Parasites. 81 

case of echinococcus cysts, bothriocephalus and taeniae*). Local 
inflammatory lesions of the skin and mucous membranes are the 
result of mechanical injuries caused by a variety of parasites. 

The amount of nutritive substance abstracted by parasites from 
the host is to be regarded as usually relatively insignificant. 
Where, however, the parasites are blood-suckers, the host is placed 
at special disadvantage; the smallest of the round worms, if pres- 
ent in large numbers, may cause serious loss of blood, and per- 
haps the death of the host. The roe, the common deer and the 
sheep, for instance, are uniformly killed by an anaemia if blood- 
sucking strongylidae infest the rennet-stomach. Whole flocks of 
poultry may die out when the poultry mite, dermanyssiis avium, 
gets into the hennery and infests the skin of the fowls in vast 
numbers, feeding daily upon the blood. 

A century ago our appreciation of the life history of the parasites 
and of the diseases caused by them was but vague. It is true that most 
of the worms found in the human alimentary canal were known to the 
students of natural history in antiquity; and as early as the seventeenth cen- 
tury itchmites and their relation with the itch were fairly well known. 
Yet it was . for the most part believed that parasites had their origin in 
inspissated juices or pathologically altered parts of the human or animal 
body by a process of spontaneous generation (generatio aquivoca). When 
the microscope came into use and it became possible to closely observe their 
generative organs and their products (eggs), and particularly after attempts 
came to be made to artificially transmit the parasites by experimental feed- 
ing of the worms and their larvse, the real history of their development was 
for the first time apprehended. Redi and Swammerdam, van Doeveren and 
Pallas, Pastor Goeze, C. Fr. Miiller, Bojanus, Abildgard, toward the end 
of the 18th and the beginning of the 19th century, Steenstrup, v. Baer, 
v. Siebold, van Beneden, Kuchenmeister, in the middle of the latter 
century, corrected the mistakes and hiatuses of the earlier views and 
investigated the most interesting parasites ; and in recent years the studies 
of a large number of zoologists, physicians and veterinarians (Leuckart. 
Zenker, M. Braun, Peroncito, Grassi, Railliet, Heller, Zurn, L. G. Neumann, 
v. Ratz and others) have contributed to extension of our knowledge in 
this field to such a degree that pathology and practical hygiene have been 
decidedly benefited by their investigations. 

♦Persons handling ascaris megalocephala. the round worm of the horse, es- 
pecially if engaged in mincing it, are apt to be directly affected by a conjunctivitis 
and urticarial eruption from a certain substance existing in the cuticle of the worm 
(apparently a dermal secretion) which possossos irritative propertlep 



82 Causes of Disease. 



TABLE OF PARASITIC ARTHROPODA OF THE DOMES- 
TIC ANIMALS.* 

I. Insects Insecta \ . 
1 — Blood-sucking Flies, attacking- the Skin. (After Neumann.) 

Culex pipiens 'and other gnats) in man. 

Simulia reptans, horse; mucous membranes of the head. 

macidatum, horse, ruminants, man. 
Tabanus boi'inus. morio. autumnalis, bromius. rusticus, fulvus, 
albipeSj horse, ruminants, man. 

Hcematopota plui'ialis, horse, ruminants, man. 

Chrysops cacuiicr.s. horse, ruminants, man. 

Stomo.vys calcitrans, horse. 

Hccmatobia stimulans, ferox. irritans, serrata. horse, ruminants. 

Glossina morsitans. horse, ruminants. 

Hippobosca equina, horse, ruminants, dog. 

Melophagus ovinus, sheep. 

2 — Flies Parasitic Upon or Beneath the Skin in larval Stage. 

Calliphora zomitoria. various domestic animals. 
Scrcophaga carnaria. magnifica, Wohlfarti. 
Lu cilia Cccsar, scricatc ellaria. 

Ochromyia anthropopliaga. dog. cat. goat. man. 
Hypoderma lineata, sheep [cow]. 

tarandi. reindeer. 

boz'is, cow i even in the spinal canal"). 

silenus. horse, ass. 
Dcrmatobia noxialis. cow. dog. 

3 — Flies Whose larvae are Parasitic in the Intestines and Body 

Cavities. 

Gastrophilus equi. stomach and pharynx of [horse]. 
pecorum. stomach. 

duodcnalis, duodenum of horse and exceptionally 
in dog:. 



•Details of the life-history and the pathological significance of the species 
enumerated may be found in Kitt's "Lehrhuch der SpesieUen Pathol. Anatotnie der 
Han-st'tif.'' [See also Friedberger and Fruhner. Veterinary Path.olont/, Amer. 
Edition, W. T. Keener & Cc CV.icago, 1904.) 



Animal Parasites. 



83 



Gastrophilus hcemorrhoidalis, stomach, rectum of horse. 

Havipes, stomach of ass. 
Oestrus ovis (Cephalomyia ovis) , nasal and brain cavities of 
sheep. 

4— Fleas. 

Pulex irritans, man, dog, cat. 

serraticeps, dog. 

goniocephalus, rabbit. 

avium, chickens, pigeons and other birds. 

penetrans, seu Sarcopsylla penetrans, man, domestic ani- 
mals (tropical). 

Sarcopsylla gallinacea, domestic fowl in tropics. 

5 — Lice. 

Hcematopinus macrocephalus, horse. 
eurystemus, cow. 
tenuirostris, cow. 
stenopsis, goat. 
" cameli, camel. 

piliferus, dog. 
latus, dog. 
ventricosus, rabbit. 

6 — Parasites of Hair and Feathers. 

Trichodectes pilosus, horse. 

parumpilcsus, horse. 
. scalaris, cow. 
sphceroccphalus, sheep. 
climax, goat. 
latus, dog. 
subrostratus, cat. 
Melophagus ovinus, vid. blood-sucking diptera. 
Goniodes dissimilis, Burnetii, Goniocotes hologaster, gigas, 
Lipeurus variabilis, hetcrographus, Menopon pallidum, biseriatum, 
all in the hen. 

Goniodes stylifer, poly trapezius, Menopon biseriatum , turkey. 
Goniodes numidianus, rcctangulafus, Lip. numidicc, Mow p. 
numidice, guinea fowl. 

Goniodes falcicomis, paniccps, rectangulatus, Menof, plnros- 
tomum, horse. 



84 Causes of Disease. 

Goniodes colchicus, truncatus, chrysocephalus, Lipeurus varia- 
bilis, Menop. production, biseriatum, pheasant. 

Goniodes minor, compar, Lip. barulus, Colpoceph. longicaudum, 
Men. latum, biseriatum, pigeon. 

Docophorus icterodes, adustus, Lipeurus jejunus, anseris, Trino- 
ton conspurcatum, continuum, goose. 

Docophorus icterodes, squalidus, Trinotum luridum, Menopon 
obscurum, duck. 

Ornithobius bucephalus, swan. 

II. Spiders. (Arachnoida.) 

1 — Mites. Parasites Upon the Skin. 

Demodex sive Acarus folliculorum canis, cati, suis, caprce, ovis, 
etc. (in the sebaceous glands and hair follicles). 

Sar copies major s. scabiei communis, in and beneath the epi- 
thelium, in horse, dog, sheep, goat, camel, monkey, man. 

Sarcoptes minor, cat, rabbit. 

Dermatocoptes communis, horse, cow and sheep ; also in goats. 
cuniculi, in ear of rabbit. 

Dermatophagus communis, horse, sheep. 
auricularum felis, cat. 
canis, dog. 
cuniculi, rabbit. 

Dermatoryctcs mutans, fowls, foot itch. 

Sarcoptes locvis, pigeons and fowls. 

Epidermoptcs bilobatus and bifurcatus, fowls. 

Harpirhynchus nidulans, pigeons, in the feather follicles. 

Hypodectes columbarum, pigeons, subcutaneous connective tis- 
sue and body cavities. 

Laminosioptes cysticola, fowls, connective tissue. 

Cystodites nudus, fowls, pheasants, air spaces, lungs, liver, 
kidneys. 

Syringophilus bipectinatus, fowls, pigeons. 

uncinatus, peacocks, quills of feathers. 

Analges minor, fowls, quills of feathers. 

Dimorphus eolumbec, pigeon. 

Leptus autumnalis, dog, man. 

Dermanyssus avium, birds, man, dog. cat, horse, cow (ear). 

Gamasus pteropoides, rabbit, mole, field mouse, cow (ear). 

Cheyletus parasitivorox, rabbit, 



Animal Parasites. 85 

2 — Ticks. (Sucking blood from skin.) 

Ixodes ricinus and hexagonus, man, dog, horse, cat, ruminants, 
birds. 

Boophilus annulatus s. bovis, cow (America). 
Dermacentor reticulatus, sheep, cow, horse, man (America). 

" electus } dog (America). 

Argas miniatus, cow. 
■Amblyomma americanum, cow, man. 
Ornithodorus Megnini, man, cow, sheep, horse, ass, dog. 
Argas reflexus s. marginatus, pigeons. 

3 — Pentastomes of the Viscera. 

Linguatula tamioides, dog, wolf, horse, goat, man (nasal pas- 
sages). 

Larval form, Linguatula denticulata (mesenteric lymph nodes, 
lungs, liver), ruminants, horse, cat, rodents. 

LIST OF WORMS PARASITIC IN THE DOMESTIC 

ANIMALS. 

I. Flatworms. 

1 — Tapeworms. 

Anoplocephala s. Tcenia plicata, horse. 
perfoliata, horse. 
mammillana, horse. 
Moniezia expansa, ruminants. 

planissima, ruminants. 
Benedini, ruminants. 
" Neumanni, ruminants. 
trigonophora, ruminants. 
denticulata, ruminants. 
alba, ruminants. 
Thysanosoma ortinoides, sheep. 

"■ Giardi, cow and sheep (hog). 

Stilcsia ccntripunctata, sheep. 
" globipunctata, sheep. 
Tcenia marginata, dog; bladder worm, cysticercus tenuicollis, 
ruminants and hog. 

Tcenia serrata, dog; bladder worm, cysticercus pisiformis, hare, 
rabbit. 



86 Causes of Disease. 

Tcenia echinococcus, dog, jackal, wolf; bladder worm, echinoc- 
occus polymorphus, man, ruminants, hog. 

Tcenia cccnurus, dog; bladder worm, ccenurus cerebralis, rumi- 
nants, horse. 

Dipylidium caninum, (Taenia cucumerina), dog, cat, man; 
bladder worm, cryptocystis trichodectis et pulicis, larvae of dog 
fleas and ticks. 

Mesocestoides lineatus (Taenia litterata), dog, fox, cat. 

Tcenia serialis, dog ; bladder worm, cysticercus s. coenurus seri- 
alis, rabbit. 

Tcenia Krabbei, dog; bladder worm, cysticercus tarandi, rein- 
deer. 

Bothriocephadus lotus, man, dog, cat ; larva, plerocercoid of 
fishes. 

Bothriocephalus cordatus and fuscus, dog. 

Tcenia crassicollis, cat ; bladder worm, cysticercus fasciolaris, 
mouse. 

Dipylidium Chyzeri, Pasquali, Trinchesii, cat. 

Tcenia solium, man ; bladder worm, cysticercus cellulosce, hog, 
dog, cat, sheep, roe, polar bear, rat, man. 

Tcenia biennis horn. s. medio canellata s. saginata, man; blad- 
der worm, cysticercus inerniis, cow. 

Drepanidiotcenia infundibidiformis, fowl. 

Dicranotcenia sphenoides, fowl. 

Davainca proglottina. 

tetragoua, cesticillus ectinobothrida, fowl; Fried- 
berg eri, pheasant. 

Bothriotcenia longicollis, fowl. 

Drepanidiotcenia lanceolata, setigera, fasciata. anatina, gracilis, 
Krabbei, tenuirostris, goose and duck. 

Dicranotcenia furcigera, megalops, coronula, duck. 

Mesocestoides imbutiformis, duck. 

Echinocotyle Rosseteri, duck. 

Davainea crassula, pigeon. 

Bothriocephalus cohimbarum, pigeons. 

2 — Fluke- worms. 

Fasciola hepatic a, distomum hepaticum, ruminants, hog, ass, 
horse, rodents, man (liver — errant examples in the lungs and 
musculature ) . 



Animal Parasites. 87 

Fasciola lanceolata, distomum s. dicroccelium lanceolatum, ru- 
minants, hog, rodents (liver). 

Fasciola magna, cow, elk [deer], (liver), (America, Italy). 

Distomum truncatum } albidum and felineum, cat (liver). 

A gamo distomum suis, hog (muscle). 

Distomum, echinostomum alatum, ducks and other water fowl, 
exceptionally dog (intestine). 

Amphistoma conicum, ruminants (first stomach). 
Collinsi, horse (intestine), (Egypt). 

Gastrodiscus Sonsinoi, horse (intestine), (Egypt). 

Monostoma verrucosum, duck, fowl, goose. 
attenuatum, goose (intestine). 

Distoma oxycephalum, duck, fowl, goose (intestine). 

dilatatum, armatum, linear e } ovatum, commutatum, 
fowl (intestine). 

Holo stoma erraticum, duck (intestine). 

Distomum hcematobium s. crassum (Bilharzia crassa), cattle, 
sheep, monkey (urinary organs, intestine), (Mediterranean bor- 
ders). 

Distomum Westermanni, cat [man] (lungs). 

Distomum heterophyes, dog (intestine), (Japan). 

Distomum pancreaticum, cow, sheep, (Japan). 

II. Round Worms. 
1 — Acanthocephalid Worms (Thorn-headed worms). 
Echinorrhynchus gigas f hog, man (intestine). 

polymorphus, goose, duck (intestine). 

2 — Common Round Worms. 

Ascaris megalocephala, horse, ass (intestine). 
mystax, dog, cat (stomach, intestine). 
" lumbricoides, man (intestine). 
" suilla, hog (intestine). 
" vituli, cow (intestine). 
" ovis, sheep (intestine). 
Heterakis maculosa, pigeon (intestine). 
" inflcxa, fowl, turkey (intestine). 

papulosa s. I'csicularis, fowl, peacock, guinea fowl, 
turkey (intestine). 

Heterakis diff evens, fowl (intestine). 

" dispar, duck, goose (intestine). 

Gnathostoma hispidum, hog (stomach). 



88 Causes of Disease. 

3 — Pin Worms. 

Oxyuris vermicularis s dog, man (rectum). 

curvula, mastigodes, horse (colon and rectum). 
ambigudj rabbit (caecum). 

4 — Strongylus Worms. 

Eustrongylus gigas, dog, horse, cow (kidneys, peritoneum, 
heart, liver). 

Eustrongylus tubifex, duck (intestine). 

Strongylus armatus s. sclevostomum armatum, horse (intes- 
tine) ; peritoneum (larva: and embryos wander into the arteries, 
brain, testes) ; sir. armatus has recently been subdivided by 
Sticker into three species: Scler. edentatum, bidentatum, quadri- 
dentatum. 

Strongylus tetracanthus (sclerost. tetr.), horse (large intes- 
tine). 

Stroiigylus coutortus, ruminants (abomasum, small intestine). 
Ostertagi } cow, sheep, goat (abomasum). 
Curticei, cow, sheep (abomasum, small intestine). 
oncophorus, cow (abomasum, small intestine). 
Harkeri, cow (abomasum). 

rctortcuforniiSj ruminants, hare, rabbit (abomasum, 
small intestine). 

Strongylus hlicollis, sheep (small intestine). 
radiatuS; cow (small intestine). 
inflatuSj cow (colon). 
Axci, ass (stomach). 
hypostomus, sheep, goat (intestine). 
tilaria, sheep, goat, fallow deer, red deer (bronchi. 
lungs). 

Strongylus paradoxus, hog, sheep (bronchi, lungs). 

connnutatus, sheep, goat, hare (lungs, bronchi). 
micrurus, cow, horse, red deer, fallow deer (bron- 
chi, lungs). 

Strongylus Arnheldii, horse (lungs). 

sagittatus, red deer (lungs). 

eapillaris, goat, sheep, chamois (bronchi, lungs). 
". dentatus, hog (large intestine). 
" rubidus, hog (America). 

annulatus (Strong, s. Filaria tracheo-bronchialis) , 
dog (air passages). 



Animal Parasites. 89 

Strongylus vasorum canis, dog (blood vessels). 
" pussilus, cat (lungs). 

" tenuissimus, horse (stomach). 

leporum, hare, rabbit (stomach), (America). 
tenuis, goose (caecum). 
" nodularis, goose (pharynx). 

s. Syngamus trachealis, bronchialis, fowl, pheasant, 
horse, goose, duck, etc. (air passages). 

Dochmius trigonocephalies, dog, cat (intestine). 
stenocephalias, dog (intestine). 
tubceformis, cat (intestine). 

bovis s. (Esopha go stoma vesiculosum, cow (intes- 
tine). 

(Esophagostoma columbianum, sheep, deer (intestine). 
Uncinaria cernua, sheep, goat (intestine). 
Ollulanus tricuspis, cat (stomach, embryos in the lung). 
Strongyloides intestinalis s. Anguillula st ere oralis, man, fowl 
(intestine). 

Anguillula vivipara, horse (colon). 
Rhabddnema longum, sheep, hog (intestine). 

5 — Whip Worms. 

Tricocephalus dispar, man, dog. 

aMnis, ruminants (large intestine). 
crenatus, hog (large intestine). 
depressiusculus, dog (large intestine). 
Trichosoma curophilum, cat (trachea, bronchi). 
felts cati, cat (urinary bladder). 
longicolle, fowls (caecum and rectum). 
annulatum, fowls (pharynx). 
contortum, duck (crop, pharynx). 
" collare, fowls (intestine). 

tenuissimum and brcvicolle, pigeon (small intes- 
tine). 

Trichina spiralis, hog, rat, man, all carnivora (intestine, em- 
bryos and undeveloped trichinellae in muscle). 

6 — Filariae. 

Filaria papulosa s. equina, horse (peritoneum, pleura ), 
terebra, cow, deer (peritoneum, eye). 



90 Causes of Disease. 

Filaria lacrymalis, horse, cow (conjunctival sac). 
immitis, dog (heart) (Asia [America]), 
s. Spiroptera sanguinolenta, dog (stomach, aneurisms, 
pharynx). 

Filaria s. Spiroptera strongylina, hog (stomach). 

s. Spiroptera megastoma and microstoma, horse (stom- 
ach) ; Gongylonema scutatvim, sheep, cow, horse (pharynx) ; 
Gongylonema pulchrum, hog (pharynx, tongue). 

Filaria s. Onchocerca reticulata, horse (tendons, ligamentum 
nuchae) . 

Filaria hemorrhagica, horse (skin). 
DermoMiaria irritans, horse (skin). 
Filaria uncinata, goose (pharynx, crop, intestine). 
nasuta, fowl (crop). 

s. Dispharagus spiralis, fowl (pharynx, crop). 
Tropidocera inflata, duck (crop). 

7 — Annelides. 

Hcemopis sanguisuga, horse (pharynx). 



COURSE AND TERMINATION OF DISEASE; 
SYMPTOMATOLOGY; DIAGNOSIS 

The disturbances of function which indicate the existence 
of disease, as well as anatomical or chemical organic changes, are 
spoken of as the signs or symptoms of disease; the branch of 
study dealing with these as semeiology or symptomatology 
(t6 a-nfxetov from <n}fxaii>w, to denote ; <rvn-irlirTetv , to happen with, that 
is, in connection with certain disease states).* 

The art of concluding from symptoms the existence of definite 
morbid changes in the body, of determining the nature and loca- 
tion of disease, is known as Diagnosis or establishment of 
a diagnosis (ij didyvwais, differentiation or thorough knowledge; 
from yiy puhtkciv, to recognize). Formerly when the anatomical 
and chemical faults which underlie disease were unknown it was 
deemed sufficient for the physician to merely appreciate the ex- 
ternal manifestations of disease, and such terms as dropsy, jaun- 
dice, fever and marasmus were used without attempt at nearer 
approach to the causes of these symptoms. Even to-day there 
may now and again be times when it is necessary to rest satisfied 
with no more than such a symptomatic diagnosis. However, as 
far as it is possible to conclude from symptoms that definite ana- 
tomical changes exist, or as far as such are directly manifest, 
we are accustomed in these days to make anatomical diagfioscs; 
and as far as it is possible to determine the development of any 
affection, to make also an (etiological diagnosis. The aim of 
modern diagnosis is the study of the disease from all three of 
these points of view and the appreciation of the condition of all 
the organs in their relation to each other, so as to permit of the 
recognition of how a given local condition must influence the 
rest of the organs of the body generally. 



•The principal features of this chapter have heen In part adapted from 
Handbuch der allgem. Pathologic, V\\\ und Wagner (Leipzig, 1S7G). 



92 Symptomatology ; Diagnosis. 

A purely symptomatic diagnosis is illustrated by such examples as 
the determination of varieties of convulsions, of palpitations, coughs ; a 
symptomatic and anatomical diagnosis, by the recognition of a relation 
existing between jaundice and some hepatic affection; an serological diag- 
nosis, by the conclusion that a jaundice depends upon the presence of 
some microorganisms in the liver and blood. [Very frequently diagnoses 
are classified as Topographical, when indicating the location and extent of 
lesions, and as nosological, when indicating the nature of the process. 
Xo diagnosis can be regarded as complete unless embodying the recogni- 
tion of both location and nature of an affection, as well as of its aetiology, 
in so far as is possible. Incomplete, purely topographical diagnoses, as 
the declaration of "lung disease/' "kidney disease," etc.. are often made 
to serve the nonce, or by the careless as final : in the same way an incomplete, 
merely nosological diagnosis is often met with where it is said that an 
individual is the subject of "inflammation,'' '"congestion," "'dropsy,*' "fever," 
"tuberculosis." The full diagnosis should declare that the subject has 
an inflammation of the pericardium, if possible indicating the cause of 
the pericarditis; "tuberculous caseation of the lungs'' would embody all 
the desirable points of view.] 

Symptoms immediately referring to changes in a given part, 
as abnormality of color, increased size, hardness, softness or un- 
evenness of outline, are spoken of as direct symptoms ; those 
which do not depend upon the diseased organ entirely, but which 
perhaps may be appreciable in the products of such an organ or 
become manifest in other organs in relation with the diseased 
part, are known as indirect symptoms. Thus a direct symptom 
of a lesion of one of the cardiac valves would be a cardiac mur- 
mur ; an indirect symptom of pericarditis would be an oedema 
of the dewlap. There are certain symptoms called pathognomonic 
symptoms, which definitely indicate the existence of some particu- 
lar disease, as the rusty nasal discharge in pneumonia, locking of 
the jaws in tetanus, crepitus at the site of a fracture of bone; 
however, as a rule a single symptom does not suffice for a diag- 
nosis, but must be considered in its relations with a wider group 
of recognized features. Study of disease phenomena constitutes 
a large part of clinical pathology and pathological anatomy ; the 
ability to recognize and to determine the importance of symptoms 
is one of the essentials of the medical art. and depends on the 
skill, experience, general knowledge and power of judgment of 
the individual conducting the examination of the subject. The 
majority of symptoms can be realized only by special methods 
of examination. He who has not acquired such methods cannot 
have a clear understanding about the morbid condition extant 
in the body of his patient, and is really groping about in the dark- 



Diagnosis. 93 

ness. Eye, ear and sense of touch, partly unaided, partly aided 
by instruments of precision and special technical methods (em- 
ployment of reflecting mirrors for illumination, of instruments 
used in percussion and auscultation, of methods of mensuration, 
weighing, thermometry, microscopy or chemical tests) contribute 
to our power of appreciation of the signs of disease. With ex- 
perience it is possible that the examiner at a single glance 
(diagnosis at a distance) may recognize some types of disease, 
some forms which manifest themselves by sharply marked ex- 
ternal features appreciable even at a hasty inspection. Other 
morbid conditions may be more or less correctly conjectured 
from the information given by some person from his observation 
of the patient (diagnosis from the anamnesis: av*-ixi\Lvr\<xKw, to 
recollect). Both methods are open, however, to serious error if 
practiced alone, being based on incomplete data and imperfect in- 
vestigation ; and although practical experience with quick per- 
ception of frequently observed facts may often arrive at the 
truth by such methods, only careful objective study will guaran- 
tee an absolutely certain diagnosis. In order to gain a compre- 
hensive idea of the pathological process presented, it is essential 
not only to consider the functional disturbances of one single 
part of the body, which is apparently the seat of the disease, but 
to systematically inquire into the condition of every part of the 
economy and every function. 

(For fuller discussion of these points the reader is referred 
to Friedberger-Frohner, Lehrbuch dcr klinischcn Untersuchungs- 
methoden, or Moller, Klin. Diag. dcr aussern Krankheiten dcr 
Hanstiere, F. Enke, publisher.) 

The art of diagnosis concerns itself, after the proper recog- 
nition of the symptoms manifested, with the condition of the 
organs, finally reaching a definite conclusion through processes 
of comparison of the features appreciated with the commonly ac- 
cepted pathology of known diseases. All possible affections are 
carefully considered, the symptoms presented by the subject con- 
trasted with those of each different known disease, and determina- 
tion of the affection attempted from the strongest features of 
correspondence. 

[In systematic study of a given case it is well to follow some 
routine of investigation. Thus commonly one takes into consider- 
ation such general features as the age, sex, race or species oi the 
subject, the general surroundings and habits of life and features 



94 Course of Disease. 

bearing on questions of heredity ; subsequently the general pre- 
vious medical history of the subject, the anamnesis, is taken up, 
and a study of the known features of the present attack in its 
development. Thereafter is made a close and complete objective 
study of the subject, this including as thoroughly as possible the 
whole body, the condition of every organ by the methods of ordinary 
physical diagnosis and the more elaborate methods of clinical 
technology. Given such data one should be able by his patho- 
logical training to recognize the seat of the affection and the 
extent of its distribution in the body, the topographical diagnosis, 
and the nature of the affection, the nosological diagnosis.] 

The establishment of a diagnosis leads directly to prognosis 
and therapeutic application. By the term prognosis is meant the 
foretelling of the mode of development [the order of the events 
in the course, and the duration of the disease] and termina- 
tion (whether favorable, prognosis fausta; unfavorable, prognosis 
infausta; or uncertain, prognosis anceps). The course and ter- 
mination of many diseases may be predicted with more or less 
certainty, inasmuch as examples of the affections are constantly 
occurring and an experienced physician is quite familiar with their 
development and modes of progress. The prognosis must, 
however, in a measure depend upon each individual case, its 
special constitutional peculiarities, the degree of general involve- 
ment of the body and the distribution of the disease-changes, the 
vital importance of the affected organ, the variations of the disease 
from its usual trend, the complications and the possibility of em- 
ploying proper remedial measures. 

Therapeutics (^ depaireia, from Bepawed, to serve or cure) or 
remedial treatment has to deal with efforts directed toward com- 
pensation for and removal of disease. Where it is possible by 
definitely conceived measures to remove the basic fault, the 
anatomical alterations and the causative influence underlying the 
morbid condition, therapy manifestly becomes rational or radical; 
where it is possible only to combat symptoms (pain, fever) it is 
said to be symptomatic treatment, which at best is but a tempo- 
rary means or measure of relief (palliative, from pallium, a cloak 
or protection). 

The duration and course of diseases depend closely upon their 
causes and upon the extent and nature of their basic structural 
alterations. Some diseases are sudden in their onset, last but a 
few minutes or hours, and terminate in the death of the individual 



Diagnosis. 95 

or in a rapid disappearance of the various lesions. The former 
type includes such conditions as wounds, lacerations of external 
or internal parts or the effects of poisons which rapidly and com- 
pletely destroy the function of vital organs ; the latter, character- 
ized by rapid recovery, is met in disturbances which are not fol- 
lowed by structural changes, as convulsions, ansemic and hyperae- 
mic states of the brain, of the skin and of mucous membranes. 
On the other hand, diseases may continue for weeks or months, or 
even years. They may begin suddenly or gradually and insidiously ; 
may manifest alternately intensity and diminution in the severity 
of their symptoms, fluctuations in the morbid processes (remis- 
sions and exacerbations) ; may invade suddenly ■ (paroxysmal; 
paroxysm, invasion) and present interruptions (intermittent) in 
the course, sometimes ending with gradual improvement (lysis, 
resolution), sometimes in a rapid, abrupt change (crisis, decisive 
stage), leading to recovery or death. [By the course of the dis- 
ease is meant the order of manifestation of the various stages or 
events of the disease. It may be definite, regular or acute on the 
one hand, when its events proceed in orderly manner and come to 
a definite termination, or it may be indefinite, irregular or chronic, 
when there is no fixed order of events and there is no set limita- 
tion. Among the different types of the regular course two major 
forms are recognized: (a) the continued course, where there is 
but little variation in the intensity of the symptoms from time to 
time, and (b) periodic courses, in which at certain definite times 
special events manifest themselves. Among the periodic courses 
are met, intermittent forms, in which there alternate periods of 
absence of symptoms, known as intermissions, with periods of 
presence of the symptoms in their intensity or paroxysms ; remit- 
tent forms, in which there alternate periods of intensity of symp- 
toms, known as exacerbations, with periods of diminution in in- 
tensity, known as remissions ; and recurrent forms in which there 
alternate comparatively long periods of absence of symptoms, the 
intermissions, with similarly prolonged periods of their presence, 
recurrences. The last form differs from the first in the length of 
the alternating periods.] 

Diseases of brief duration are called acute diseases; those of 
prolonged course, chronic. The former may last for a variable 
period, up to fourteen daws, while the latter extend over a course 
of more than forty daws; any instances falling between these 
durations may be classed as sub-acute affections. In ease of 



g6 Course of Disease. 

diseases which ordinarily continue, for a year or more, a shorten- 
ing of the course to a few months manifestly fixes such duration 
as an acute one, as in case of tuberculosis, glanders or rickets. 
[The terms acute and chronic have really a less limited signifi- 
cance than the author here applies to them ; they each have in one 
sense a reference to the length of the course, but in addition refer, 
perhaps without desirable clearness, to the possibility of recovery 
and the intensity of symptoms and the order of events in the 
course. In the matter of time it is scarcely possible to give any. 
fixed number of days, or even months, to the terms. Each dis- 
ease is a law unto itself, and only in the broadest way may we 
say that an acute course is one of brief duration. But in addi- 
tion, when we apply this term, we mean that whatever the actual 
duration, at any rate the disease will come to a definite limit ; and, 
moreover, we expect the course to follow more or less closely a 
given order in the manifestation of its symptoms, and believe 
there is a chance of recovery. In case of chronic diseases again 
we cannot set a fixed limit of days, months, or even years, which 
shall declare the course to be a chronic one? (Thus, while alienists 
are inclined to set a limit of a year to cases of mania or melan- 
cholia, and to call all cases chronic if of longer duration, there 
really are no appreciable differences in many instances of even 
longer duration from their condition within the first few weeks of 
insanity.) Moreover, when a case is declared chronic, while 
there is no actual assertion to this effect, nevertheless there is a 
feeling of hopelessness as to the chance of recovery ; the termina- 
tion looked for is rather death, and that at an indefinite time. No 
exact order of symptom presentation is expected in such chronic 
cases. Finally, while there are often exceptions to this point, 
in general the severity of the symptoms of an acute case is apt to 
be greater than in a chronic form of the same disease.] 

Diseases often show [especially those of an acute, regular or 
definite type of course] a succession of definite periods or 
stages in which certain phenomena appear, which are empirically 
expected and whose development is awaited with the progression 
of the anatomical changes. These diseases are said to have a 
typical course. [A regular or definite course is well illustrated by 
the acute infectious fevers, in which the following periods may 
be recognized in the order named: (a) infection (time of en- 
trance of the microbic cause), (b) incubation (a period without 
symptoms, but during which the germs are multiplying in the 



Stages of Disease. 97 

economy to sufficient number to excite their definite effects), (c) 
prodromes (a period of indefinite and usually slight symptoms, 
the first and as yet more or less obscure evidences of the presence 
of microbes in the system), (d) invasion (the period of develop- 
ment of the specific symptoms of the affection ; this, if it occur 
rapidly, is said to be a frank invasion; if gradually, is called an 
insidious invasion), (e) acme or fastigium (the period of fullest 
intensity of the disease), (f) occasionally an amphibolic stage (a 
period of uncertainty and marked variation, corresponding to the 
popular idea of crisis and used by the author above in this sense), 
(g) decline (period of disappearance of the disease; this, if it 
occur rapidly, is said to be "by crisis;" if slowly, "by lysis"), (h) 
finally, not as a true stage of the disease, but a definite period 
before health is resumed, convalescence (period of repair and re- 
building of structures destroyed or impaired in the course of the 
affection, and of resumption of efficient function by the various 
parts of the body). If the cause of an acute disease be not a 
vital one the course includes, of the above stages, only those of 
invasion, acme, decline and convalescence.] 

However, in such well-known affections, as a result of special 
serological factors or the accidental interference of external in- 
fluences, variations (irregularities) may occur, rendering the 
course an atypical one. In case the symptoms remain for a long 
time of uniform type and intensity, without appreciable ameliora- 
tion or increase, the disease is said to be stationary. 

Latent diseases are those which do not manifest themselves, 
either at all or in part, in certain phases of their development. 
This depends upon either the impossibility or difficulty of proper 
examination of the organs, which are the seat of the disease (as 
the pancreas or some parts of the lung), or upon the fact that the 
disease is so localized or has been so gradual in its development 
that the function of the organ has not been materially affected. 
Latency is often, therefore, only a temporary or transient feature, 
and it is often correct to speak of a latent stage and of a later 
manifested or open stage. Some diseases, even though they be 
severe, remain latent because they are followed by adaptations 
(compensatory conditions) which entirely prevent their usual 
symptoms, as when a valvular lesion of the heart is followed by 
compensatory cardiac hypertrophy. 

When a disease is characterized merely by local symptoms and 
alterations it is known as a local disease or disease of [this or 



98 Course of Disease. 

that] organ; if, however, a number of organs are involved and 
their functions interfered with, and if the general economy is ap- 
parently affected, the condition is spoken of as a general disease 
or a disseminated (generalized) disease. (Examples of general 
disease are met with in such alterations as provoke general 
metabolic disturbances and abnormalities in the composition of the 
blood. Formerly the term constitutional disease or dyscrasia, de- 
composition of the blood, was used in this connection.) Funda- 
mentally there is no distinction in these terms, but as a rule the 
term dissemination has special reference to a multiplication of 
local lesions, to an extension of the causes of the disease to a 
number of situations where new foci of the same type appear, or 
to a reaction of a functional disturbance of one organ upon the 
rest of the system. For example, a prolonged disturbance of the 
function of the kidneys will give rise to a disturbance in the 
cardiac action and retention of harmful products of metabolism ; 
or, as in the case of tuberculosis, the infectious agencies pass 
from the original local fecus into the lymph and blood, extend by 
direct growth into the surrounding organs, and in various scat- 
tered foci in the body to which they have been conveyed ; the dis- 
ease thus becoming disseminated and generalized. Some affec- 
tions, on the other hand, at first manifest general symptoms 
(fever), later, however, showing distinct evidence of their purely 
local type. Variations in the course of disease may also depend 
upon the predisposition characterizing the animal species in ques- 
tion, as, for example, is seen in case of glanders in field mice, an 
acute septicemic affection, in contrast to the same disease in 
horses, where it is usually a chronic local affection, gradually ex- 
tending through the system. 

The local lesions which first arise from the operation of a 
pathogenic agency are known as primary lesions, those which fol- 
low as secondary. The action of such an agency may be confined 
to one locality, the lesions disappearing after its removal, as in 
case of corrosion, heat action or traumatism. The generalization 
usually depends directly upon the spread of the pathogenic influ- 
ences through the body, and may therefore take place (1) by 
continuity and contiguity of the tissues (per continidtatem, per 
contiguitatem) , (2) by the blood or lymphatic tissues (hematogen- 
ous, lymphogenous) , and (3) as already referred to, the func- 
tional interdependence of one organ upon the others may, in case 
of disease at one point, lead to further change in other parts of the 



Extension of Disease; Termination of Disease. 99 

system (sympathetic or consecutive lesions). By the term exten- 
sion by continuity is understood the progress of the pathological 
process upon the surfaces in continuity and along uninterrupted 
tissues in the immediate vicinity of the original focus, as along 
the mucous membrane of the nose to the frontal and maxillary 
sinuses, from the pharynx to the Eustachian tubes and middle 
ears. Extension by contiguity occurs from one surface to that of 
an adjacent organ in contact with the first, as from the visceral 
pleura to the costal pleura, from the serous surface of the stomach 
to the liver. The explanation for such a mode of extension is 
mainly to be found in the fact that the pathogenic agent finds 
some particular opportunity for invading such adjacent tissues ; 
thus bacteria may pass to an adjoining structure, be swept along 
by its fluids and spread widely. A suppurative or gangrenous 
focus in the lung may in some such manner gain access to the 
pleura ; the latter may rupture and the microorganisms, spread 
over the entire pleural surface from the respiratory movements, 
may give rise to an extensive pleuritis. Hematogenous extension 
of a disease occurs when the pathogenic agents gain access to the 
blood ; lymphogenous extension, when such influences, through 
the agency of the wandering cells, are mingled with the lymph 
(cf. embolism). Sympathetic disturbances in function are appar- 
ently in part the result of sensory and motor reflex action, in 
part the result of primary changes, the efficiency of one organ 
depending upon the functional integrity of another, as a chronic 
hepatic cirrhosis induces cardiac hypertrophy and splenic cyanosis 
by the circulatory disturbances which it produces. 

Coincidence of diseases may occur entirely independently of any 
relation between the processes, or may depend upon some connec- 
tion ; where this occurs complications are said to exist. Thus 
swine-erysipelas is often complicated by valvular endocarditis (the 
infectious germs invading the latter structures), or suppurative 
osteitis of the cranium may be complicated by a meningitis 
(through extension of the suppuration by contiguity to the 
meninges). 

The termination of disease may result in one of three ways : 

1. Recovery, cure or restoration, complete re-establishment 
of the disturbed function and condition of the organ : 

2. Incomplete recovery, with appearance of secondary affec- 
tions, persistence of sequels or defects ; or 

3. Death of the individual. 

LOFC. 



ioo Termination of Disease. 

Termination in recovery is accomplished through the repara- 
tive powers natural to the economy. The body is possessed of a 
variety of regulative mechanisms, whereby the influence of harm- 
ful agencies is neutralized, the loss of chemical substances and 
tissues is repaired, and noxious materials are eliminated from the 
system. Such processes may in a compensatory fashion correct 
this or that fault, as by the discharge of toxic matter from the 
stomach or intestines, the removal of the products of fatigue from 
the muscles and nerves through the blood and lymph, the expul- 
sion of exudations from the lungs through expectoration. Many 
corpuscular disturbing factors (as bacteria, dead cells, hsemor- 
rhagic foci) are removed through the activity of the living cells 
(phagocytes) and digested, the body being thus freed of such sub- 
stances. Other foreign bodies are encapsulated by a wall formed 
by the tissues of the organism for their own protection, and thus 
rendered harmless. Deficiency of nutritive material in the fluids 
and cells is corrected by the supply from the stomach and intes- 
tine ; dead cells are replaced by new elements from existing forma- 
tive areas (as new blood cells from the bone-marrow). Tissue 
losses are repaired by processes of regeneration. And, too, the 
production of antibodies of most varied type is possible for the 
protection of the animal body. 

The therapeutic art is in no wise at variance w T ith natural proc- 
esses of recovery, but, on the contrary, employs the various regu- 
lating and compensatory mechanisms of the body in order to bring 
about an adjustment of the disturbances, and attempts to induce 
conditions more favorable to a rapid adjustment than is possible 
when no influence is brought to bear upon the pathogenic agent ; 
at the same time it attempts to restrain further agencies which 
may retard the recovery. The practice of medicine is also 
directed to guard against the extension of contagious diseases and 
particularly against the inception of disease, so that in this phase, 
too, the lofty power of science holds nature in check, which, with- 
out the aid and skilled intervention of man. would threaten with 
annihilation, all too soon, the creatures of the earth. The signifi- 
cance and success of medical science is particularly impressed 
upon one when it is recalled how destructive epidemic diseases, 
which in times past carried off millions of animals and men, have 
in some instances been wholly eradicated, in other instances greatly 
diminished. By appreciation of the nature of a varied group of 
affections, there has come the discovery of efficient methods for 



Termination in Recovery; Death. 101 

their cure and for prophylaxis against them. Of course, no rem- 
edy has been found for death, the inevitable end of development 
of all living beings, and the laws of nature can by no medica- 
ment, whatever its power, be broken. Yet the skillful use of the 
means of nature may hold off premature death and may assist the 
injured body to regain its health. Medical art can prevent fatal 
haemorrhages, it loosens adhesions, cuts away what is unfit, 
dilates narrow canals, has antidotes at its disposal, can procure 
rapid evacuation of the bowel or emesis, remove foreign objects 
from the body, relieve promptly nervous strain, alleviate pain 
directly, often correct irregularity of cardiac action, reduce dan- 
gerous temperatures and accomplish a multitude of services with- 
out which a given disease might well end unfavorably or be 
protracted over a tedious course. 

After recovery begins at the close of a general affection, there 
occurs a period, known as convalescence, the subject still evincing 
muscular weakness and marked sensitiveness to external influences. 
[During this period there are taking place various reparative and 
reconstructive processes in the economy, looking to the restoration 
of altered and destroyed elements, and, too, functional efficiency is 
being re-established, and all remaining factors of the previous 
disease are being finally eliminated from the system.] 

Recovery is regarded as incomplete where, after a disease has 
run its course, there persist in the economy conditions preventing 
normal functional efficiency of the organs or where there is evi- 
dent some permanent impairment of tissue [sequela: of disease]. 
As illustrative of this may be mentioned deformities of bones, 
cicatricial strictures of canals, kinks of the intestines, pericardial, 
pleural or other adhesions by bands of connective tissue result- 
ing from the previous disease, opacity of the normally transparent 
media of the eye, palsies of muscles and nerves, or the defects 
left after ulceration or burns. 

Termination of disease in death (exitus lethal is or Ictalis, 
from letum, death ; from A^e-q forgetfulness, \avddvco to make forget- 
ful) occurs when the organs which subserve the most important 
and necessary processes of vitality suspend their function. Inas- 
much as continuance of life depends in an important measure 
upon the uninterrupted supply of blood containing oxygen to the 
medulla oblongata through the action of the heart, underlying which 
must be recognized the necessity for respiratory movements regu- 
lating the efficiency of the pulmonary surface in the intake of 



102 Termination of Disease. 

oxygen and output of carbon dioxide, it is essential to accept as 
causes of death of primary importance, various lesions and func- 
tional disturbances of the hind brain, the heart and the lungs. 
These parts are therefore spoken of as the atria mortis. Inhibi- 
tion of their functions may be a direct result of chemical, me- 
chanical or electrical influences (as from poisons which destroy 
or paralyze the nerve cells, concussion, the action of lightening), 
or may indirectly follow a wide variety of factors interfering 
with tissue nutrition, metabolism and gaseous interchange (anae- 
mia, albuminous waste, closure of respiratory passages, elevation 
or depression of body-temperature, reflex palsies). The more 
important modes, therefore, by which this or that disease may 
induce death, are : 

i. Cessation of cardiac action, caused by toxic or reflex nerv- 
ous paralysis of the cardiac ganglia, fatigue and degeneration of 
the cardiac muscle, cardiac rupture, complete obstruction to the 
escape of blood from the cardiac chambers (formerly known as 
exit us lethalis per syncopem, ovv-Kfareiv, to strike together). 

2. Asphyxiation, from interference with intrapulmonary 
respiratory interchange of gases, obstruction of the lungs or upper 
respiratory passages, compression of these tubes, spasm or palsy 
of the respiratory muscles, diaphragmatic rupture (exitus lethalis 
per suit o cat ion em). ■ 

3. Medullary Paralysis, or paralysis of the respiratory centre 
in the medulla oblongata, from circulatory interference at the 
base of the brain, influence of toxic substances upon the nerve 
cells, concussion of the brain or reflex influences (exitus lethalis 
per apoplexiam, a.-* oifk-fi a aecv, to strike down). 

4. Hemorrhage, from rupture of important vessels, or ex- 
travasation of large amounts of blood into the somatic and 
visceral cavities. 

5. Exhaustion, from inanition or consumption (diminished 
nutrition and exaggerated metabolism, accumulation of fatigue 
products and poisonous metabolites, auto-intoxication). 

These modes of death may, of course, complicate each other 
and may be mutually causative of each other (as when haemor- 
rhage induces ischaemia of the heart and coronary vessels, with 
the result of cardiac cessation and at the same time the symptoms 
of suffocation, due to an anaemia of the medulla). Senile debility, 
more or less complicated by various diseases, is also to be re- 
garded as a cause of death (senile marasmus, from fxapaiveiv, to 



Termination in Death. 103 

weaken), a natural and necessary termination for each individual 
cell and for the entire cellular complex. In the individual cell, as 
well as in all the tissues of the organism of higher animals, 
changes are continually proceeding which lead to the destruction 
of the living substance and sooner or later result in the death of 
the individual. The living multinucleated organism is continually 
losing cells by their death, the substance of which is eliminated 
from the economy with the excretory material or is broken up and 
re-employed by the system. From causes inherent in the organ- 
ism itself, but at present impossible of clear definition (vid. Ver- 
worn: Geschichte des Todes ; Allgem. Physiologie) the power of 
multiplication ceases in the individual groups of cells and organs 
in varying rates in the different species of animals, and with vary- 
ing swiftness the characteristics of old age and of death become 
apparent. Perpetual youth, immortality in the sense of reproduc- 
tion, always renewing themselves, is possible only for the conju- 
gated sexual cells (propagation cells), while in case of the somatic 
elements (and those sexual cells failing of copulation) the vegetal 
force sooner or later disappears. Whenever the decay of cells of 
vital importance reaches the grade in which it distinctly interferes 
with the rest of the economy, the mutual relations of the various 
parts is disturbed, and death ensues, just as a clock stops when 
its wheels wear out or are broken. 

Transition from life to death may occur suddenly (mors subi- 
tanea) ; the animal falls from its standing position to the ground, 
becomes unconscious, and for a few moments at most is thrown 
into convulsions with groaning respirations. Such sudden termi- 
nation may be noted in death from lightening stroke, sun stroke, 
rupture of the heart, cerebral concussion, massive internal haemor- 
rhages or cardiac and cerebral paralysis. In the majority of in- 
stances, however, death comes on gradually, with the manifesta- 
tion of characteristic phenomena which predict the termination of 
life, and which together constitute what is known as the death- 
agony (77 aywvla, the struggle, death struggle). They include the 
signs of a progressive paralysis of the nervous and muscular sys- 
tems, together with those of the disease which causes death. 
Animals in the agonal state are unable to raise themselves from 
the ground, usually lie flat on one side, from time to time lifting 
the head and letting it fall heavily to the ground, with the feet 
rigidly extended and moved convulsively, at first violently, but 
gradually more and more weakly. Respiration is slowed and 



104 Termination of Disease. 

labored, deep groaning respirations following at irregular inter- 
vals the ordinary shallow breathing. With the appearance of pul- 
monary oedema, rales, heard even at a distance, are produced by 
the fluid exudate beaten into a foam in the air passages (death 
rattle). Involuntary discharges occur from the bowel and blad- 
der, when paralysis of the sphincter muscles develops. The heart 
beats more rapidly, but the relaxed arteries are no longer able to 
propel the blood forward and the pulse in consequence, although 
quick, grows small and finally indistinguishable, and the skin is 
cool. The hair is bathed with a clammy sweat. The body tem- 
perature in the agonal period in diseases accompanied by loss of 
blood or inanition falls considerably below normal (hypothermia, 
to 36-35 ° C), while in other types there may be an ante- 
mortem rise in temperature. Extinction of life means complete 
cessation of metabolism, of cellular growth and the existence of 
the individual ; and death therefore manifests itself by complete 
termination of the functions of all parts of the body. The last 
breath, naturally in the form of expiration, and the moment of 
complete cessation of the heart may ordinarily be looked upon as 
marking the actual end of life. However, the organs do not all 
perish at precisely the same moment; after the last breath the 
heart may flutter a few minutes ; and after death from haemorrhage, 
peristaltic movements of the intestines may sometimes be ob- 
served for perhaps fifteen minutes ; and similarly after death from 
electricity muscular contractions may be elicited as long as rigor 
mortis does not set in (one to three hours after death). 

The following are the characteristic signs of true somatic 
death : 

1. Muscular rigidity (rigor mortis), sometimes setting in im- 
mediately after death, sometimes only after four to twenty hours 
later, and depending upon the coagulation of the muscle albumen. 
The muscles in this change become set, shortened and thickened, as 
in vital contractions ; the extremities are rigid and either cannot 
be flexed or only with the application of considerable force, and 
the mouth cannot be opened by ordinary traction upon the lower 
jaw. After twenty-four hours, or perhaps later, the rigidity 
disappears [due to decomposition]. 

2. Cadaveric fall of temperature (algor mortis) develops in 
from half an hour to twenty-four hours after death, varying with 
the surrounding temperature and the degree of metabolic activity 
prevailing at the time of the death agony. In some affections, as 
in tetanus, because of the important heat production caused by the 



Signs of Death. 105 

muscular contractions and because after death heat dissipation 
falls on account of the cessation of the circulation in the peri- 
phery of the body, a post-lethal internal temperature rise, to 
perhaps 42-44 C, occurs, persisting a number of hours. 

3. The eye in death: The eyelids of the cadaver are usually 
half open (rigidly) ; the ocular bulb is sunken and somewhat less 
tense than in life (evaporation of some of its fluids) ; the cornea 
becomes dull and opaque ; the pupils are dilated. The ocular reflex 
movements upon touch are entirely absent. 

4. Appearance of putrefaction: The bacteria in the digestive 
tract, producing all sorts of fermentative changes in the contents 
of the canal, shortly after the death of the tissues, penetrate the 
latter and cause their putrefaction. The gases, produced in large 
quantities from the fermentative processes, dilate the stomach and 
intestines, causing abdominal distension, sometimes to such a 
degree as to force the lower bowel out of the anus, rupture the 
diaphragm and allow the intruding intestines to distend the chest. 
The advance of putrefaction may be noted in the colorless parts 
of the skin by greenish discolorations (sulphur compounds of 
haemoglobin), and also by the foul odors of cadaveric decomposi- 
tion. These changes cause the disappearance of the rigidity of 
the body and progress the more rapidly the warmer the surround- 
ing temperature. Measures which inhibit the growth of the 
putrefactive bacteria, preservation in alcohol or formaline (injection 
of the vessels with antiseptic or balsamic substances), refrigera- 
tion, drying, prevent putrefaction. With the advance of putre- 
faction all the organic matter of the body is broken up into 
ammoniacal compounds, carbonic acid and water, with the forma- 
tion of a great variety of by-products (putrefactive alkaloids, 
acids, gas-forming matter, etc.) until finally only the solid calcified 
bones remain. 

The name apparent death is applied to a condition in which all 
the vital functions are depressed to the lowest possible degree, 
when only by great care in the examination of the seemingly dead 
body can there be detected feeble cardiac contractions and occa- 
sional faint respiratory movements, a condition accompanied by loss 
of consciousness and sensibility, and by reduction of the body 
temperature. In recently born animals this condition is seen com- 
paratively frequently, lasting perhaps fin- hours (asphyxia neona- 
torum) ; in this connection it is perhaps due to a premature separa- 
tion of the placenta, aspiration of the amniotic fluid, compression 
of the umbilical cord, or to anaemia. 



DISTURBANCES OF CIRCULATION 

Life and health are possible for the organs only if there be 
unimpaired circulation of a blood capable of supplying oxygen 
and nutrition to them. Disturbances of the circulation, as well as 
faults of the blood and lymph, in other words, deficiency in the 
provision and passage of good blood through the organs, endanger 
both life and health. 

The normal heart possesses a notable adaptabilty to the varying 
demands upon its capacity for work ; it accommodates itself im- 
mediately to the current of blood entering it by virtue of the elas- 
ticity of its walls ; regulates the energy and rhythm of its contrac- 
tions in conformity to the amount of blood in its chambers, the 
general circulatory resistance and the demand for blood in the ac- 
tive or resting organs. This power of accommodation enables it, to 
a certain extent, to overcome and compensate for pathological dis- 
turbances affecting the hsemic circulation ; under such circumstances 
there is said to take place a compensation for these disturbances. 

Where such conditions of resistance to the heart's action are 
of slow development and permanent, a thickening of the myocar- 
dium is assumed in connection with the increased requirement for 
work, consisting essentially in an increase in the number and size 
of the muscular elements (cardiac hypertrophy). It may be 
said that even physiologically the size and muscular strength of the 
heart are adjustable to the demands made upon it in its function 
as a forcing-pump or as a suction pump. Certain animals, for 
example, which in the course of their lives perform especially 
intense muscular work, are likely to exhibit hearts larger in pro- 
portion to the body-weight than animals accustomed to but little 
muscular activity.* Pathological hypertrophy differs from this 
physiological form only in its cause, in the latter the excessive 
work being but a natural and customary condition in the life of the 
animal, in the former the result of abnormality of the vascular 

*See also Kitt, Lehrbicch der pathol. Anatomie d. Haustiere. II. Aufl. 



Cardiac Hypertrophy. 107 

system, of excessive blood pressure and of unusual quantities 
of blood within the organ. Such "work-hypertrophy" of the gen- 
eral organ is met in connection with epicardial adhesion to the 
parietal pericardium, compression of the base of the heart from 
pleuritic adhesion, tumors or similar conditions, because in such 
cases the propulsive effort of the entire organ has a greater oppo- 
sition to overcome. 

Hypertrophy of one side of the heart is seen especially in case 
of valvular lesions. These valvular lesions involve irregularities 
in the closure of the orifices of the heart and its great vessels ; 
they are of two types, either narrowing of the orifices from pro- 
liferative changes, bloods clots, etc. (stenosis), or incompleteness 
of closure of the orifices by the valves (valvular insufficiency) . 
Stenosis at the aortic opening increases the work of the left ven- 
tricle in order that the blood may be forced through the narrowed 
orifice, and in proportion there ensues a work-hypertrophy of the 
left ventricular wall. Following stenosis at the origin of the pul- 
monary artery there occurs a work-hypertrophy of the right heart 
(sometimes dilatation after special preceding strain). Valvular 
insufficiency also leads to hypertrophy, because where the valves 
are incompletely closed there first occurs a tendency to stasis 
because of the back pressure of the blood (regurgitation), which is 
likely to induce ventricular or auricular dilatation, and therefore 
the heart is required to work the harder in order to propel the larger 
quantity of blood. Although the so-called compensatory hyper- 
trophy of the heart does in some measure contribute to the regula- 
tion of the blood distribution and is of some service, yet in reality 
it is only the expression of an increased blood-pressure in one of 
the ventricles or auricles or in the afferent or efferent vessels, and 
the compensation which it induces is only a relative one. As a 
matter of fact, the increase of pressure persists and the circulation 
does not become normal (Krehl). Even when the animal is 
at rest the continued heightened blood pressure causes the develop- 
ment of dilatation of the capillaries, pulmonary passive congestion 
and distension with consequent diminution in the pulmonary excur- 
sion, together with difficulty in breathing. The arteries show dis- 
tinct changes of the pulse, the vessels being unusually tense and 
distended; they eventually lose their elasticity and may rupture. 
A very large heart may in addition mechanically interfere with 
the lungs. These consequences are still more evident if the indi- 
vidual exercises physically, the muscular exertion raising the blood 



108 Disturbances of Circulation. 

pressure still higher. (Powerful muscular contractions force 
larger amounts of blood into the right heart ; the ventricles become 
engorged and the haemic pressure rises.) Eventually the heart 
loses its force as a pathological hypertrophy is not, as might be sup- 
posed from the thickness of the walls, capable of indefinite response 
to increased functional demands, but on the contrary, is often 
unable to accomplish even the more moderate requirements made 
upon the strength of the heart. Perhaps the reason for this is that the 
influences which give rise to cardiac hypertrophy at the same time 
harm the myocardium in other respects. For example, valvular 
lesions, causing the heart to become hypertrophied in their train, 
are frequently caused by infectious substances. Such agencies may 
also cause a myocarditis ; and if the inflammation be protracted and 
of low grade, it causes considerable reduction in the efficiency of 
the muscle. Moreover, the conditions which cause pathological 
cardiac hypertrophy are typically not stationary, but on the con- 
trary the circulatory difficulties are apt to progress (the stenosed 
orifices are likely to become still more narrowed, thrombi which 
interfere with the vascular lumen become larger, capillary areas 
become contracted) ; and from such extra demands upon its ability 
the heart becomes fatigued. There must eventually, therefore, suc- 
ceed upon compensatory hypertrophy a period of failure of com- 
pensation, a period of broken compensation. [There are numer- 
ous influences which combine to limit cardiac hypertrophy and to 
determine its eventual loss of compensatory power, and so certain 
and uniform are these results that it might well be declared a law 
that every pathological hypertrophy of the heart must necessarily 
reach a limit to its enlargement and must thereafter fail in its power 
of compensation and undergo degenerative changes. The limita- 
tions, aside from those set by the age of the muscle and its inher- 
ent power of increase, depend mainly upon the amount of proper 
blood which the coronary vessels are able to supply. In a 
great measure this is determined by the original size and construc- 
tion of these vessels, although doubtless there is a possibility of 
true hypertrophy in these so as to accommodate the growing needs 
of the enlarging organ ; yet if the original cause of the hypertrophy 
were a widespread arteriosclerosis the coronary arteries would 
be extremely likely to have been involved. Even were this not 
true, the mechanical influence of a hypertrophied left ventricle 
upon the walls of these vessels in close functional and topograph- 
ical relation with the pumping action, and the similar influences 



Cardiac Failure. 109 

of the aortic recoil after closure of the aortic valve, must favor 
the development of a local coronary sclerosis on account of the 
possibility of fibrillary injuries to the walls. Given an arterio- 
sclerosis there is every reason to expect an imperfection of the cor- 
onary circulation from the narrowing of the lumen and the in- 
creased rigidity of the tubes ; and with the imperfection of circu- 
lation thus fixed upon the myocardium, its nutrition and ability 
to further enlarge are necessarily limited. The functional de- 
mands progressing, fatigue, degeneration and cardiac failure are 
the necessities of a not distant future.] 

Diminution of cardiac force is spoken of as cardiac failure, 
cardiac insufficiency. It follows various influences affecting the 
myocardium or its ganglia, among which as prominent examples 
may be mentioned excessive exertion or fatigue, numerous poisons 
and the analogous substances present in the system in the infectious 
diseases, diminution in the blood supply to the myocardium, in- 
flammations and degenerations of the muscle, excessive fatty de- 
posits of the heart, and atrophy of the myocardium. All patholog- 
ical changes which occasion cardiac insufficiency are followed by 
disturbances in the movement and distribution of the blood. A 
fatigued and weakened heart is incapable of normal contraction, 
expels from its chambers a smaller amount of blood than normally ; 
in consequence the arteries are not properly filled, the blood press- 
ure sinks in them and the movement of the current is slowed. The 
aspirating power of a weak heart is also low and the blood moves 
less freely from the venous side of the circulation, the veins becom- 
ing engorged and the pressure raised. The results of these irregu- 
larities differ somewhat as the left or right heart alone or the 
whole organ is especially involved ; in one case the lesser circula- 
tion, in the other the greater being the more disturbed. Many 
variations, too, are occasioned by the grade of cardiac insufficiency 
and by the nature of the original causes (cf. anosmia and hyper- 
tvmia). The myocardium being weak the cardiac cavities do not 
contract as in normal conditions, contain an excess of blood, and 
this engorgement gives occasion for dilatation of one or both sides 
of the organ. 

Left ventricular insufficiency determines imperfect filling of the aorta 
and its branches, and in consequence deficiency in the amount of arterial 
blood going to the brain, skin, glands and elsewhere. The heart, however. 
remains full and the blood is dammed back into the pulmonary veins, and 
the right heart experiences marked difficulty in forcing the blood through 
the lungs, jnsufficience of the right heart, on the contrary, causes inoQm 



no Disturbances of Circulation. 

plete filling of the pulmonary artery, pulmonary anaemia, and, of course, the 
left heart in its turn receives unduly low amounts of blood. In the right 
auricle and larger veins engorgement and tension become marked, tending 
to cause a passive engorgement of the venous system throughout the body, 
a cyanotic liver, cyanotic spleen, etc. 

A heart reduced in its propulsive power is itself but poorly 
supplied with blood because its own arteries are but incompletely 
supplied. Any condition of fatigue which prevails may there- 
fore easily become exhaustion, complete functional inability, arrest 
of cardiac action (cardiac paralysis, cardiac syncope, cardiac col- 
lapse). All these terminal changes interfering with circulatory 
integrity are occasioned by any influences which impair the con- 
tractile efficiency of the myocardium, any agencies which either 
directly or indirectly reduce its muscular power (rupture, fatty 
degeneration, inflammation, prevention of expansion of the heart 
from some external interference, anaemia) ; in the same way the 
action of some paralyzant toxine upon the cardiac ganglia, the 
analogous action of thermic and electric agencies, excessive reflex 
stimulation of the vagus or of the vagus nucleus in the medulla 
oblongata (the latter from deficiency of the blood oxygen, 
increased blood pressure in the brain, or toxines). 

Just as in cases of diseases of the heart, affections of the 
arteries and veins are apt to occasion irregularity of distribution 
and movement of the blood in given organs and areas of the 
body. Narrowing of the arteries from vasoconstriction (arterial 
spasm), thrombus formation, inflammation and permanent shrink- 
age raise the intracardiac blood pressure and occasion dilata- 
tion and hypertrophy; the organ to which such a. constricted 
artery is distributed is imperfectly supplied with blood and a 
variety of changes may in consequence occur in it (cf. ancumia 
and embolism). Decrease in the elasticity of the vascular walls 
or paralysis of the arterial musculature permits the vessels to 
dilate, the current to become slowed and the organ, congested. 
Reduction in the muscular tonus of the vessels of the splanchnic 
area from vasomotor paralysis, usually from toxic and infectious 
influences, causes a massive congestion of the abdominal vessels ; 
in consequence of which the general- blood pressure falls, cardiac 
labor from the small amount of blood coming to the organ ensues, 
and there is a fatal collapse (Krehl). 

In the veins interference with the progression is occasioned 
not only by cardiac weakness, cardiac lesions and pulmonary 



Hyperemia and Anosmia. in 

affections which interfere with the aspiration factor of venous cir- 
culation and by thrombosis of the veins ; but it should also be kept 
in mind that any abnormal compression of these thin-walled veins 
must interfere with the return flow of blood. The nearer the 
heart such compression occurs the greater the harm to the gen- 
eral body. Compression of the two venae cavae, which from the 
compressibility of these vessels is quite possible from pleural effu- 
sions, induce a reduction in the amount of blood entering the 
cardiac chambers and A^enous congestion throughout the economy 
(cf. hyperemia) . 

The lymph supply and drainage are in close relation 
with the abnormalities of the blood vascular system and blood 
circulation ; imperfections in the lymphatic circulation give rise to 
abnormal accumulations of fluid in the lymph vessels and serous 
cavities and occasion a wide group of organic lesions. 

Local Variations in Amount of Blood. Hyperaemia and Anaemia. 

The amount of blood in the organs of even healthy individuals 
is always subject to change and variation. The vessels are elastic 
tubes which are expanded by greater internal blood pressure and 
adjust themselves as their contents diminish. This is not merely 
a passive accommodation, however ; they are capable of active 
contraction and dilatation through the power of the smooth muscle 
in their structure, such alterations of lumen being primarily under 
control of nervous influences. The total quantity of blood in 
the body, similarly subject to continual variation, is never so great 
as to completely fill all the vessels were they fully dilated ; there 
exists, however, a moderate fullness, varying here and there in 
the organs as the blood-current meets resistance to its progression 
or as the blood is drawn into special organs from dilatation of 
this or that vascular area. The quantity of blood in the organs, 
and the hsemic distribution in the body generally, physiologically 
accommodates itself to the existing demands. More blood enters 
an organ when functionating; the amount traversing it dimin- 
ishes during periods of rest. The nervous stimulus which causes 
an organ to actively functionate, at the same induces dila- 
tation of its vessels, and in consequence a rich supply of blood is 
afforded. This is especially recognized in muscle. Ranke 
determined the blood content of the general musculature of rab- 
bits at rest to be 36.6 per cent, of the total muscle bulk, and noted 
this proportion nearly doubled (66 per cent.) when the muscles 



112 Disturbances of Circulation. 

were thrown into tetanic contraction. (Internal organs like the 
brain or intestine may thus be relieved of excess of blood by 
muscular movements.) When the stomach and intestine are filled 
with food during digestion they are much richer in blood than 
when empty. The influences which give rise to this stimulation 
are variable and multiple, acting sometimes directly upon the 
muscular coats of the blood vessel wall and the nervous apparatus 
inherent in the wall, sometimes upon the vascular centre in the 
medulla oblongata (mechanical, thermic, electric, chemical irri- 
tants). 

It is but a step from the physiological to the pathological, and 
there is no sharp line of differentiation ; change in the amount 
of blood in a part becomes a pathological condition when it occurs 
in an improper place, or at a wrong time, or if it exceeds the 
normal variations. 

Increase in the quantity of blood in a part of the system, local 
engorgement, hyperemia, may be of one or other of two types, 
the result either of an excessive influx of blood to the part, or of 
a diminished escape of blood from the part. 

The first form, the basic feature of which consists of excessive 
entrance of arterial blood into the tissues, is spoken of as active 
hyperaemia, or, synonymously, as irritation-hypcrccmia, congestive 
hyperemia, fluxion of blood or arterial hypercemia. Increased 
supply of arterial blood may be caused by excessive blood pressure. 
This is met where an artery is occluded or some part of the body is 
for some reason prevented from receiving its proper supply ; under 
which circumstances the blood propelled from the heart passes 
into the adjacent structures (collateral hypercemia) , that is it 
rushes into the pervious branches of the artery near the obstruction, 
under the influence of the higher pressure. As a rule, however, 
instead of the blood being forced into the part in question, there is a 
lowering of the vascular tension, spoken of as a relaxation in 
the arterial distribution (rela.ration-hypercemia) , with a resultant 
widening of the channels. The blood freely pours into the dilated 
arterial branches and capillaries, and with increased force; in a 
word it is drawn into the part. The degree of relaxation depends 
largely upon the lack of tone of the smooth muscle of the vascular 
wall and the congestion is therefore in such instance a my o paralytic 
one. Every muscle being inseparable from its innervation, nervous 
influences must finally be regarded as responsible for changes in 
the vascular tension (tone). It is assumed that the vascular 



Active Hyperemia. 113 

nervous apparatus comprises two types of nerve fibres, vasodilator 
and vasoconstrictor ; theoretically, therefore, stimulation of the 
vasodilator nerves should occasion a widening of the blood chan- 
nels (neurotonic congestion), and the same result should follow 
paralysis of the vasoconstrictors (neuroparalytic congestion), both 
of these influences similarly reducing the tension of the muscular 
elements of the arterial wall. This relation with nervous influ- 
ences is well seen in the fact that after section of, the cervical 
sympathetic in rabbits the ear on the corresponding side becomes 
hyperaemic (CI. Bernard), and after section of the splanchnics the 
vessels of all the abdominal viscera become distended and engorged 
with blood (paralysis of the vasoconstrictors). Stimulation of the 
nervi erigentes of the human penis causes a dilatation of the 
arteries of the organ ; blushing in man is brought about by psychic 
influences upon the dilator centre through reflex action ; certain 
poisons, as nicotine and alcohol, are apparently stimulating to 
the dilator centre. Generally the stimulation or paralysis of the 
vascular nervous apparatus indicated is the direct result of local 
influence by physical or chemical agents. Thus hyperemia may be 
induced mechanically by the removal of pressure acting upon the 
vessels ; just as a sponge which has been squeezed and is then 
released takes up water, so the blood flows in large amount, imme- 
diately after removal of the pressure, into a tissue which has been 
deprived of its blood for a long time because of compression. The 
vessels here do not at once regain their contractility, but are 
relaxed. 

Similarly friction and scratching can induce hyperemia 
mechanically, from the nervous stimulation thus originated. 
Thermic influences of both types give rise to hyperemia ; heat by 
its direct relaxing influence upon the vessel walls, cold first 
causing a vasoconstriction which later gives place to a paralyysis 
of the vascular musculature. There is a special group of chemical 
irritants as oil of mustard, cantharides, ammonia, alcohol, chloro- 
form, ether, saline solutions, which, either by stimulating or 
paralyzing the nerves of the vessel walls, cause a more or less 
intense arterial hyperemia ; these, because of the value of the 
hyperemia in the treatment of various affections, arc of therapeutic 
importance (rubefacients, drugs which cause reddening of the 
skin). Probably in the erythemata which occur in various infec- 
tious diseases there also exists a similar toxic stimulation <>r 
paralysis of tne vessel walls either from the bacteria or the 
microbic products. 



H4 Disturbances of Circulation. 

Active hyperemia is essentially an arterial and capillary dilata- 
tion. The hyperaemic organ or tissue therefore manifests as one 
of its features a red color, which is the more striking the paler the 
tissue normally is, as in mucous and serous membranes, and may 
be so pronounced that the distended arteries appear as fine deep- 
red lines (branched or injection erythema). The rapidity of the 
flow of the blood into and through the involved area, with but 
little output of its oxygen, causes it to remain bright red and 
pass thus into the veins. In peripheral parts of relatively lower 
temperature previous to the increased blood supply, there is a rise 
of temperature up to that of the blood. These peripheral parts, 
particularly the skin, because of their greater heat loss and their 
comparatively poor blood supply are lower in temperature than the 
internal organs ; but with the access of more blood of the body 
temperature the skin with its rate of heat dissipation unchanged 
necessarily becomes warmer. The temperature attained does not, 
however, exceed that of the internal organs ; and these, should they 
become hyperaemic, do not suffer any increase of temperature. 
Where there is marked capillary distension, provided the tissues 
are not rigid, there may also be induced some swelling. 

The results of arterial hyperaemia vary with its duration and 
location. Hyperaemia of the brain is followed by unimportant or 
marked disturbances of consciousness, dizziness and general excita- 
tion (pressure of the engorged vessels on the nervous elements). 
Hyperaemia of the sympathetic nerve does not cause either lachry- 
mation or salivation, and it is doubtful whether an uncomplicated 
hyperaemia causes any special lymph formation. In case of long 
continuance of the hyperaemia there becomes apparent an increased 
tissue proliferation ; this is probably not due to the increased blood 
supply alone, the irritant which underlies the condition having also 
in all likelihood some stimulative influence in its causation. 

As a rule uncomplicated hyperaemia is a transitory condition ; 
with the disappearance of the cause for the vascular relaxation the 
contractility of the arteries returns. Otherwise the hyperaemia 
may be regarded as the precursor and concomitant of inflammation. 
Where large amounts of blood are drawn into extensive areas of 
hyperaemia, a deficiency of blood (collateral anaemia) may be occa- 
sioned in other regions. 

Where the excess of blood exists in a part because of difficulty 
in its exit from the part it is known as passive hyperaemia or 
venous engorgement. This condition is encountered in connection 



Passive Hyperemia. 115 

with low arterial pressure, the blood not being properly propelled 
through the capillaries, in connection with deficiency in the pro- 
pelling power of the heart and arteries or complete loss of the 
arterial reactions {atonic hyperemia). When the blood is not kept 
moving onward, in compliance with the law of gravitation it set- 
tles into the dependent parts of the body. As the animal lies on 
one side the lowest parts become the seat of special engorgement 
(one half the lungs in the cadaver). This hypostatic or gravita- 
tion hyperemia {hypostasis) takes place because of the longer 
persistence of the blood in fluid condition in the capillaries as 
compared with the larger vessels. It may be noted in animals 
unable to raise themselves from the ground in long protracted 
diseases or in the agonal period, and may also develop after 
death. It may, however, develop in a nondependent organ because 
of reduction in its arterial supply, particularly if the blood pressure 
in the venous trunk be so great that the blood presses back from 
the veins into the capillaries no longer filled from the arterial 
side. Since the progression of the blood in the veins depends 
in part upon general muscular movements and the passage of 
blood from the venae cavae is particularly favored by the inspira- 
tory expansion of the thorax, deficiency in body movements and 
in respiratory activity (pulmonary diseases), as may be expected, 
promote the development of hypostatic congestion. The most 
common obstacle to the venous circulation arises from compression 
of the delicate walls of the veins by external pressure, kinking as 
in intestinal volvulus, constriction or pressure from tumors ; reduc- 
tion of the venous lumen or actual obstruction from thrombosis 
should also be mentioned in the same connection. 

Passive congestion of the portal vein and its branches, affecting 
the spleen, stomach and intestines [and pancreas] is occa- 
sioned by all diseases of the liver accompanied by shrinkage or 
reduction of the capillary network of the organ, the condition 
interfering with the progression of the portal blood through the 
liver. 

Widespread passive hyperaemia is met in case of cardiac valvu- 
lar lesions because of the interferences offered to the ready move 
ment of the blood from the venae cavae and pulmonary veins. 

A passive congestion caused by local interferences may have no 
further results provided the venous tnmk in question or its tributar} 
capillaries communicate by collateral circulation with other veins 
which are not affected, the blood then passing freely through such 



n6 Disturbances of Circulation. 

collateral anastomoses. This readily occurs if such paths are at all 
numerous and large; and where they are of narrow calibre they 
are gradually widened by the pressure of the obstructed blood, so 
that even very small branches and capillaries come to assume con- 
siderable dimensions permitting the blood to escape from the area 
of obstruction practically unhampered (anastomotic compensation). 
The possibility of such dilatation depends, however, upon the degree 
and rate of development of the venous obstruction and requires 
time. In the case of sudden venous obstruction and the existence 
of few anastomotic channels, before the collateral branches can 
adapt themselves to the congestion the disturbance of the circula- 
tion may well induce important functional and vital changes in the 
affected organs ; and, of course, such occurrences are to be ex- 
pected if the obstructed veins have no communication with other 
unobstructed channels (portal vein, the veins of the kidneys and 
lungs). Even compression under the finger (in phlebotomy or in 
a rabbit's ear) will show how the impeded blood causes the veins to 
dilate and swell up ; all the rest of the phenomena of this form of 
hyperemia may be followed up experimentally in the exposed 
tongue of a frog or under the microscope, after the ligation of 
the larger venous trunks so that the blood can pass out only 
through the venules. The web of the frog's foot may be employed 
for the same purpose after ligation of the femoral vein. At first 
the blood in the engorged and expanding veins and capillaries 
becomes slowed, then irregular, now flowing forward, now back- 
ward, and sometimes stagnates totally. It can be seen that in 
some places the current is reversed, that the blood is passing 
out of the engorged area through the collateral branches, these 
gradually dilating, and the stationary or slowly moving corpuscles 
gradually being drawn into the current and after a time the proper 
rate of circulation again assumed. 

If a number of veins are occluded or cut off sufficient to entirely 
or largely prevent collateral compensation, stagnation or stasis of 
the blood takes place. In the affected parts of the vessel the red 
blood corpuscles are packed so closely together that their outlines 
can scarcely be distinguished and the blood completely fills the 
vessel as a uniform red mass. Stasis becomes especially well 
marked if, while the venous outlets are completely closed, the 
blood continues to be forced in from the arteries. The capillaries 
dilate to their fullest ; their walls, permeable to the plasma even 
before their distention, can no longer hold the fluid blood, but allow 



Passive Hyperemia. 117 

it to escape more or less freely according to the pressure, and may 
in fact, rupture. However, even if the blood be not forced into the 
area from the arteries, exudation of the fluid part of the blood 
through the distended capillary walls may take place in ordinary 
atonic hypostatic congestion, and there may even occur a diapedesis 
of red blood cells. The endothelium and vessel walls remain intact 
only while they are being continually bathed with moving blood ; and 
as soon as the circulation stops it may be accepted that a disturb- 
ance of the endothelial nutrition exists, these cells then shrinking 
and causing comparatively large open interstices, through which 
exudation takes place. For these reasons passive hyperemia has 
frequently associated with it a congestion-transudation and haemor- 
rhage. The latter may be sufficiently severe to make the whole 
tissue dark red in color, infiltrated and completely occupied by 
blood (hemorrhagic stasis, hemorrhagic infarction). 

The pressure occasioned by the distended vessels and the fluid 
exudate, together with the impediment to circulation, may be fol- 
lowed by cessation of function of the affected tissues and finally 
by their. death. The longer the blood remains in the capillaries, 
slowly giving off its oxygen and capable of but little or no renewal, 
the darker it becomes ; the tissues in venous hyperemia are there- 
fore of a dark bluish red (cyanotic) hue. Such a tir,t (diffuse 
cyanosis, black erythema) may be encountered (in hogs) extending 
over practically the whole surface of the body in case of general 
passive hyperemia. The lack of oxygen and the excess of carbon 
dioxide in the venous blood are partly responsible for the functional 
disturbances arising from passive hyperemia of the various organs ; 
these conditions act by stimulating the medulla, and occasion 
dyspnoea, dizziness, convulsions, disturbances of consciousness, 
muscular weakness and fatigue. 

The superficial external parts of the body, when passively con- 
gested, become cool because of the impeded circulation of blood 
through them, because the blood is cooler than normal and the heat 
dissipation not diminished. 

In contrast to what has been said above, a mild but persistent 
passive hyperemia is apt to cause not only a swelling of the organ 
affected (kidneys, lungs, liver, spleen) because of the permanent 
engorgement and distention of the capillaries, but in addition may 
induce an increase in size and induration from the production of 
an excess of connective tissue in the part (Cf. hypertrophy). 



n8 Disturbances of Circulation. 

Stasis and stagnation of the blood may at times be caused by substances 
which act by inducing a withdrawal of the fluid elements and thus a 
thickening of the blood (chemicals acting upon vessel walls). [This can 
well be shown experimentally by bathing the mesentery of a frog, arranged 
for demonstrating the blood current, with a hypertonic saline solution, a 
rapid exosmosis of fluid taking place and the current being soon entirely 
checked, with the vessels choked with corpuscles.] 

Deficiency of blood in an organ may be part of anaemia 
of the general body (general oligaemia or anaemia ; d priv., 6\iyos, 
little, and al/xa, blood) or a consequence of local impediment to the 
blood current (local anaemia, ischaemia, from fox etv , to limit or 
check). The blood supply to any part may be impeded by: 

1. Pressure upon the part (compression ancemia) from in- 
crease in the bulk of adjacent organs, accumulations of fluid or any 
other compressing influence upon the part from without, or by nar- 
rowing of the capillaries by fat deposit, fluid or air in the paren- 
chyma of the organ. 

2. Narrowing, occlusion or fault of contractility of the arteries. 
Here may be mentioned external pressure upon the vessel, ligation, 
occlusion by solid bodies as by thrombi in the arterial lumen (cf. 
thrombosis and embolism) , rigidity of the vascular walls from cal- 
cification or sclerosis and spasm of the arterial musculature with 
resultant contraction of the lumen (arterial ancemia or ischcemia, 
occlusion ancemia, spastic ancemia). 

3. In addition, anaemia may involve a certain part of the body 
in case the general blood distribution is irregular because the gen- 
eral volume of blood passes to one large area to the deprivation 
of other parts (collateral ancemia); as when the posterior parts of 
the body are markedly infiltrated with blood (symptomatic 
anthrax) the fore parts are rendered anaemic, or as when internal 
haemorrhages occur the flesh is left anaemic, etc. 

The organ or tissue deprived of its blood looks pale, the absence 
of the blood tint permitting the peculiar hue to become more appar- 
ent and more like the tissues of slaughtered animals or like a 
washed tissue deprived of its blood by the washing. It contains 
less fluid and but little blood appears on the sectioned surface, and 
its volume is diminished because of the emptiness and collapse of 
the vessels. 

Anaemic parts at the exterior of the body, being exposed to the 
air and losing their heat, feel cool, because with the loss of blood 
their principal thermal substance is lost and they are capable of 
producing little or no heat in themselves under the circumstances; 



Local Ancemia ; Hemorrhage. no, 

and with the existing diminution of nutritive and secretory sub- 
stances disturbances of nutrition and diminution of functional 
aoility must ensue. In addition the products of previous meta- 
bolic activity necessarily remain in the anaemic tissue and may act 
unfavorably upon it. According to the grade of oxygen depriva- 
tion, need for nutrition and rapidity of metabolism in the affected 
structure there must sooner or later result a gradual death of the 
anaemic part, because of the absence of blood. It should be kept 
in mind, too, that the integrity of the endothelial lining of the 
blood vessels depends upon the continuous flow of blood through 
the vessel and that these cells gradually degenerate and become 
permeable when the anaemia is complete. Should the blood again 
flow through such capillaries which have been empty for perhaps 
twenty-four hours it readily escapes through their walls, with con- 
sequent haemorrhagic infiltration of the surrounding tissues. 
(After interruption for as much as two hours the renal epithelial 
cells become necrotic and consequently the renal function becomes 
checked or ceases entirely.) Suspension of activity in vital organs 
because of anaemia is a matter of extreme gravity. Cerebral 
anaemia is quickly followed by unconsciousness; and because of 
degeneration of the central nervous tissue, even after but brief 
periods of anaemia, this condition in the brain and spinal cord is 
likely to give rise to destruction of the ganglion cells and focal 
lesions with symptoms of paralysis. Complete anaemia of the myo- 
cardium necessarily causes cessation of the heart's action. 

Other parts of the system, as the skin and muscles, are less sen- 
sitive to the effects of anaemia ; their tissue may withstand the 
condition for some hours, as may readily be appreciated by the 
practice of artificially causing an anaemia in surgical operations by 
means of the Esmarch's elastic bandages. In case of such resistant 
parts, if the cause of the anaemia be eliminated the results may be 
but transient or only partial, as in case of the anaemia of cramps 
(spastic anaemia) or anaemia caused by external pressure. Ob- 
struction of an artery, and more particularly the anaemia resulting 
therefrom, may be corrected if the blood supply can be quickly re- 
established through the anastomotic vessels (so-called collateral 
paths). 

Loss of Blood; Haemorrhage. 

The escape of blood from the vessels into the tissue spaces, 
body cavities or to the free surfaces of the body is known as 



120 Disturbances of Circulation. 

bleeding, haemorrhage (atpa, blood; payds, rupture) or extravasation 
( extra, without ; z'as, vessel). 

The most common causes of haemorrhage are wounds and 
lacerations of the vessel walls. Anything which severs the con- 
tinuity of the vascular wall by puncture, incision, tearing, con- 
cussion or contusion affords opportunity for the effusion of blood 
{traumatic hemorrhage). In the same way all conditions which 
impair the resistive strength of the vessel walls to the pressure 
of the blood favor haemorrhage, as the lesions caused by the 
action of corrosive fluids, fatty degeneration of the walls of the 
vessels, vascular inflammations leading to brittleness and fragility 
of their tissues {corrosion hemorrhage , spontaneous hemorrhage) . 
Exaggeration of blood pressure (increase of pressure from sud- 
den and powerful cardiac contraction and from hyperemia) per- 
mits the rupture of these weakened vessels, or perhaps even nor- 
mal pressure may be sufficient. Rupture of the liver is not infre- 
quently met with from such a cause after fatty degeneration of its 
vessels and tissues. Or when the muscle of an artery (after 
chronic inflammation) is in a degenerate state its walls may be 
distended to form permanent dilatations [aneurisms] ; here the wall 
comes to consist of but little more than connective tissue, which 
tears when the distension becomes great. 

Haemorrhages of the types mentioned are spoken of as haem- 
orrhages per rhexin (£$■«, rupture; p-qyvwai, to burst through), or, 
particularly where the wall has been weakened by pathological 
changes, as haemorrhages per diabrosin {bia-^pw<xKeiv, to eat 
through). 

The blood may, however, leak out of the smaller vessels, 
capillaries and veins, without the apparent existence of any lesion 
in the continuity of structure, because of some abnormal perme- 
ability of their walls. Such haemorrhage is known under the 
names diapedcsis, or haemorrhage per diapedesin (from 8ia-T7)5av, 
to burst through). The increased permeability of the vessel wall 
is explained by the fact that under the influence of toxic, infec- 
tious, thermic or other injurious agencies, as well as from marked 
engorgement and distension of the capillaries (passive hyperaemia, 
stasis), the cement substance between the endothelial cells becomes 
porous ; for example, the endothelial cells may shrink into globular 
form and separate from each other, or openings may result 
from destruction of the cells. The red corpuscles then slip 
through between the cells or are forced out along with the plas- 



Hemorrhage \ 



121 



matic exudate ; because of their elasticity these corpuscles are 
easily able to pass through the most minute clefts of the cement 
substance. There exist therefore in these cases minute micro- 
scopic tears. Haemorrhage by diapedesis, however, may assume 
important proportion and may be fatal because of its location (as 
in the brain or stomach) or of its duration. 

Since it is the bathing of the endothelium with normal 
blood which is essential to its integrity, it may be easily appre- 
hended that even a temporary interruption of the circulation to 




Fig. 1. 

Mesentery of the dog. (a) Haemorrhage by diapedesis. (b) Ecchymosis 
occurring in a similar manner, the opening in the wall of the capillary 
having closed up again. The figure also shows an emigration of leucocytes. 
Magnified 250 times. (After Thoma.) 

the capillaries may render them abnormally permeable and be the 
cause of diapedesis after restoration of the flow (<i. embolism). 

Haemorrhages are also classed according to the type of vessel 
from which the blood escapes, as arterial, venous and capillary 
hecmorrhazes ; where the blood oozes from a widely diffused fault 
in the softer tissues, as in the liver, and the type of the bleeding 
vessel cannot be made out, the term parenchymatous hemorrhage 
is appropriate. 

The blood may escape freely to the exterior of the body or 



122 Disturbances of Circulation. 

into one of the internal body cavities {external and internal hemor- 
rhage, surface hemorrhage and hemorrhage into a cavity). When 
the exuded blood fills the tissue spaces and completely saturates 
the tissues, the terms hemorrhagic infiltration or hemorrhagic in- 
farction (infarcere, to stop up or fill up) are applied, the latter term 
being used particularly when the blood coagulates in the tissue 
and remains in it as a dense compact mass [usually in a definite 
circumscribed area of infiltration further described in connection 
with embolism] . If the bloody effusion causes an extensive, 
loose, gelatinous swelling of the tissue, diffusely filling the 
structure [applied particularly to infiltration beneath some sur- 
face], it is spoken of as a suffusion {suifundcre, to pour) or 
suggillation. Small circumscribed foci of haemorrhage, apparent 
as spots and points from which the blood cannot be discharged 
by pressure (especially in serous membranes), are called hemor- 
rhagic maculosa, ecchymoses [xvnovv, to overflow), petechie (from 
pidocchio, louse or its bite; or from pcdiculcc flea-bites [petigo, 
eruption]), or vibices when in streaks (vibcx, a streak). When 
the extravasated blood collects in a rounded mass, as when it 
dissects up the capsule of an organ or a connective tissue 
structure, or when it accumulates in a cavity or becomes 
encapsulated by a surrounding inflammatory zone, the mass 
is spoken of as a hematoma (blood boil) or hemorrhagic cyst. 
Special terms are also employed for these effusions of blood 
depending upon their location : an extravasation of blood into the 
pleural cavity is termed hemothorax; into the peritoneal sac, 
hemocelia ( noCkia, the body cavity) ; into the pericardial cavity, 
hemo pericardium; into the uterus, hematomctra (/xrjTpa, uterus) ; 
into the sac of the tunica vaginalis testis, hematocele (ktjXt], rupture). 
In addition special names have always been made use of in con- 
nection with haemorrhage from special organs : epistaxis ( eTn-aTdfriv, 
to drip) for nasal haemorrhage; hematuria (ovpov, urine) for the 
escape of blood with the urine ; hematcmesis ( e/j.e?v, to vomit) 
for gastric haemorrhage (also melena, ^eXcu^a voaos, from /xAas, black, 
because of the dark brown color given the blood by the gastric 
juice) ; hemoptysis (wTveiv, to spit) for expectoration of blood from 
the lungs; metrorrhagia for haemorrhage from the uterus; 
hemorrhagic apoplexy (aToirXeaaeiv, to strike down, to stun) for 
spontaneous haemorrhage of the brain. 

Symptoms and Results. From its characteristic blood tint an 
effusion of blood is easily recognizable anatomically as a dark red 
accumulation of blood, or spot which cannot be effaced and which 



H&morrhage. 



123 



is more or less sharply circumscribed. Upon surfaces or in the 
body cavities the extravasation presents a striking picture, in 
profuse, partly coagulated, partly fluid masses, or in a gelatinous, 
red, jelly-like tumor ex- 
tending into the loose sub- 
cutaneous or sub-mucous 
tissue (haemorrhage fol- 
lowing contusions of the 
abdominal walls, hemor- 
rhagic stasis of the in- 
testinal mucous mem- , 
brane), or sharply outlined 
in numerous definite drop- m 
like flecks (not effaced on m 
pressure) as seen in the " 
sub-serous cellular tissue 
of the pleura, pericardium 
and epicardium. In the 
secretions it is easily ap- 
preciated by the more or 
less pronounced blood tint 
which it imparts to them ; 
the intestinal contents may 
assume a slightly reddish- 
gray, cafe-au-lait color up 
to a chocolate brown or 
pure blood-red from the 
admixture of blood ; the 
gastric contents a sepia- 
brown, the urine a blood- 
red to black ; the expecto- 
rate and nasal secretion a 
rusty, red-streaked or 
foamy red appearance 
(pulmonary cedema). 

While it is usually easy 
to detect the ruptured ves- 
sel in case of massive 

haemorrhages (as a ruptured aneurism, the eroded stump d( a ves- 
sel in haemorrhage from gastric ulcers), and the infiltration of 
blood surrounding the lesion in the organ points to the origin 
of the haemorrhage and indicates its intravital occurrence, 




Fig. 2. 

Hematoma o\' the spleeD of horse, 



124 Disturbances of Circulation. 

vet in capillary diapedesis from a mucous membrane, as the gastric 
or intestinal lining, the points of escape are invisible to the naked 
eye, and only the blood deposit on the surface and the pallor of the 
mucous membrane indicate the fact of extravasation. Arterial 
haemorrhages are recognized in living animals by the bright red 
color of the arterial blood, by the spurting character of the escaping 
stream from the larger arteries, the spurts corresponding to the 
cardiac contractions ; while the bleeding from the veins is con- 
tinuous and without pulsation. However, an arterial spurting may 
be prevented by the interposed parenchyma (Samuel). If the larger 
vessels between the point of haemorrhage and the heart be com- 
pressed the haemorrhage will diminish if it be arterial ; it will be 
increased if venous. 

The results of h&morrhage depend upon the quantity and the 
duration of the bleeding, as well as the location of the lesion. In 
case of loss of over one-third of the total volume of blood (about 
3 to 4 per cent, of the body weight : the average total quantity 
being from one-tenth to one-twentieth of the weight of the body), 
the flow continuing, the blood pressure falls. The vessel walls, 
although capable of wide adaptation to the volume of blood within, 
have become too wide for the diminished amount and cannot longer 
advantageously propel it. A general oligaemia has been established, 
indicated by the pallor of the mucous membranes, dizziness, faint- 
ing f anaemia of the brain) and convulsions, and the animal may 
bleed to death. These results occur not only when the haemorrhage 
is external, but also in copious haemorrhages into the intestinal 
lumen, peritoneal cavity, etc. (internal haemorrhage). 

Haemorrhage gradually ceases by the closure of the opening in 
the vessel from the formation of a blood coagulum in the opening 
(adhesion thrombus), the closure being facilitated by constriction 
of the vascular lumen (contraction of the wall), external pressure 
(by the tissue engorged with blood), and by the fall of blood 
pressure. After such cessation the volume of the fluid portion of 
the blood is soon restored. The watery element first passes into 
the vessels from the tissues and for a time the blood is conse- 
quently more fluid ( hydraemic) than before the haemorrhage ; but 
gradually the blood cells regain their normal numbers as their 
regeneration I cf. chapter on regeneration') proceeds in the blood 
forming organs. 

At the site of haemorrhagic infiltrations the tissues present more 
or less functional alteration. The presence of the extravasated 



Hemorrhage. 125 

mass of blood exerts a certain amount of pressure and in conse- 
quence the cells and tissues are forced apart, displaced by the in- 
vading blood; and hollow viscera are occluded by the coagulated 
blood. Even small haemorrhages in the brain, according to their 
precise location, occasion a loss of function in the area affected, 
perhaps even to the extent of complete obliteration of conscious- 
ness ; in the case of spinal haemorrhages palsies ensue ; haemorrhage 
under the mucous lining of the air passages (fracture of the 
trachea and larynx) forces the same into the lumen to such a 
degree that the air passage is constricted and death from asphyxia 
may result. 

The escaped blood usually coagulates, precisely as the blood in 
venesection (cf. chapter on thrombosis). Should this clot remain 
in the tissue or in one of the serous sacs it acts as an inflammatory 
excitant ; it attracts the leucocytes by chemotaxis and causes a 
limiting zone of connective tissue proliferation about it. This 
gradually forms a capsule about the collection of blood, transform- 
ing it into a haemorrhagic cyst, often called a haematoma, in which 
the disintegrating blood exists, partly as soft, elastic, fibrinous 
masses, of a reddish or brownish color, partly as liquid serum ex- 
pressed from the clot. Such haematomata, sometimes approaching 
the size of a human head, are not infrequently seen in the spleen 
of domestic animals, around the kidneys in swine, and in the pelvic 
cavity of cattle as the results of contusion haemorrhages. On the 
other hand the penetration of leucocytes to the mass and the pro- 
liferation of fibroplastic and angioplastic tissue leads to the resorp- 
tion of the blood. Its disintegrating elements are taken up by 
the amoeboid cells and carried away ; the plasma is absorbed by 
the cells and may pass off through the lymph paths. The red 
corpuscles both in the tissue lymph and in the blood vessels begin 
to swell and lose their color or to become shriveled. The coloring 
matter, haemoglobin, having been dissolved out may soak through 
the tissue diffusely or may become deposited in the form of flakes, 
granules or more rarely as crystals through the tissue. The 
crystalline form is especially apt to occur where the blood has been 
stagnant (haematoma), appearing as ruby-red to brown, minute 
rhombic plates and needles (iron-free haematoidin) ; the granules 
are yellow and angular, sometimes give an iron reaction (hemosi- 
derin), sometimes undergo a change like the crystals by which the 
iron is separated from the haemoglobin, iron-free haMnattmhn 
(haemofuscin) remaining. 



126 Disturbances of Circulation. 

This blood precipitate is found microscopically not only at the 
site of haemorrhage, especially in the amoeboid cells which are 
loaded with it, but also in the nearest lymph glands which are often 
found tinted all through by a rusty, reddish-brown color from the 
quantity of blood pigment conveyed to them. In the dead body, on 
account of sulphur products (sulphuretted hydrogen) of the 
cadaveric bacteria, the site of a hemorrhagic infiltration may be 
found changed to a slate gray to black hue by the sulphur com- 
binations ; in life, too, in places where similar bacterial accumula- 
tions and fermentations occur (intestine, abscess cavities, fistulous 
paths, mycotic diseases of the bladder) the pigment may undergo 
the same changes in color and thereafter remain as evidence of 
previous haemorrhage. 

Dropsy, Hydrops and Oedema. 

Excessive accumulation of the tissue fluid or lymph in the 
lymph spaces, lymph vessels and serous sacs (lymph sacs) is 
spoken of as dropsy, hydrops (from adup, water) or hydropsia, 
and, if the accumulation has occasioned swelling of the tissue, as 
oedema (from oJSav, to swell). The process itself is described as 
a dropsical transudation (from sudor c, to sweat) ; the accumulated 
fluid as a transudate. Neither the process nor the transuded fluid 
is essentially anything more than a quantitative disturbance of 
physiological lymph-production. Lymph is originally derived from 
the blood, and is regarded by many as a secretory product of the 
endothelium of the capillaries, although the blood pressure is also 
maintained as a factor in its production and accumulation, affecting 
the filtration of the liquid part of the blood through the capillary 
walls. [Whether the physical processes of dialysis and osmosis 
should also be invoked here is debated. Lazarus-Barlow, in dis- 
cussing the vital transudation of lymph, urges the importance of 
tissue demands for lymph both for purposes of nutrition and for 
its influence in diluting and removing various products of their 
metabolic activities or of their degeneration, and points out that 
in this last case there exists a possible explanation for the per- 
sistence of an cedematous process in case the excretory organs as 
the kidneys fail of eliminating from the blood the various waste 
materials. Thus if, in a case of nephritis, the blood becomes sur- 
charged with waste materials and if at the same time such waste 
in a local area of special activity or of degeneration is excessive. 



Dropsy. 127 

the tissue demands for increased transudation are increased in 
order to accomplish its removal by the lymph; yet if the blood 
already contain an excess of the very substance in question the 
increased transudation only serves to more nearly complete a 
vicious cycle, and adds to the existing accumulation.] Two 
reasons may be assumed for the pathological increase of this 
fluid in the tissues, either an obstruction to the lymph drainage, 
or an unusual, exaggerated transudation ; both of which factors 
may be operative at the same time. In view of the free anasto- 
mosis and the great abundance of lymph channels, together with 
the fact that lymph absorption is also accomplished by the capil- 
laries and veins, obstruction of isolated lymph channels, it may 
be said, does not ordinarily occasion lymph stasis. Even in case 
of unusual formation of lymph there is no essential reason for 
determination of any abnormal condition, as within certain limits 
the paths of lymphatic drainage are capable of accommodating 
and carrying off large quantities of fluid, provided the tissues 
retain their proper elasticity (Landerer), and the propulsive 
forces (muscular movements, etc.) are of normal functional ex- 
cellence. It is only when the increased transudation becomes ex- 
treme and the lymphatic flow fails to keep pace, that cedema 
develops. 

The most common cause for such fault is passive hyperemia. 
In case of passive congestion the blood pressure in the capillaries 
becomes raised and the current of blood slowed, as a result of 
which the endothelium of the walls of the capillaries becomes ab- 
normally permeable and in consequence the fluid element of the 
blood exudes profusely. This exudate is usually not as rich in 
albumen as the normal lymph. As examples of cedema of this 
type may be suggested that caused by compression (as cedema 
of the lips by application of twitches to a horse's mouth), by 
venous thrombosis, by cardiac lesions which impair the current 
of blood in the vena? cavae, by pulmonary changes which prevent 
proper progression of blood from the right heart, by structural 
faults of the liver causing obstruction of the portal capillaries and 
producing portal congestion (dropsy or cedetha from passive 
congestion). Coincident interference with lymphatic drainage 
may be determined perhaps by the pressure of fluid accumulations 
in the thoracic or peritoneal cavities upon the thoracic duct, per- 
haps by the loss of natural elasticity of the tissues, stretched and 



128 Disturbances of Circulation. 

distended by the increased and persistent pressure of the lymph- 
atic transudate. 

Increased transudation is observed also in connection with in- 
flammation and changes of the vascular walls caused by toxic 
chemical agents acting either locally or. when circulating in the 
blood, widely (irritative or inflammatory dropsy). One should 
recall in this relation the influence of the slowing of the blood 
current and vascular dilatation, together with possible shrinkage 
and separation of the endothelial cells, combining to render the 
vessel walls more permeable ; moreover, a number of poisons, as 
some of the products of metabolism, seem to directly stimulate 
the endothelium to increased secretory activity, to possess what 
might be called a "lymph-driving*' (lymphogogne) action. In 
addition it may be pointed out that in inflamed tissues the lymph 
flow is impaired by the fact that the inflammation occasions 
coagulation of the lymph and impairs the elasticity of the tis- 
sues. Such features explain the occurrence of oedema around 
tissues which are the seat of purulent or hemorrhagic inflamma- 
tion (collateral oedema). 

Dropsy is often concurrent with wasting diseases and abnormal 
states of the blood characterized by poverty of its cellular ele- 
ments and increase in its proportion of water, the so-called 
cachectic or liydrconic oedema, as seen in cases of pulmonary 
verminosis, fluke disease of the liver and chronic parenchymatous 
nephritis. It is an open question in such cases whether the es- 
sential fault in determining the dropsy is the dilution of the 
blood which may perhaps make it filter more readily through the 
vessel walls, or whether we should ascribe it to the presence of 
metabolic products and other toxic matter in the circulating 
blood impairing the vascular endothelium and permitting the 
transudation because of an increased permeability. (Cohnheim 
and Lichtheim failed to obtain dropsy by introducing large quan- 
tities of sodium chloride solution into the blood of experiment 
animals, even when as much as half of the blood was replaced 
by the saline solution ; Gartner, however, succeeded in causing 
an oedema in dogs by long continued infusion of salt solution.) 

Xo satisfactory explanation exists for the rather common 
congenital anasarca of aborted calves. According to the investi- 
gations of L. Franks the thoracic duct is sometimes missing in 
these "water calves" ('or "Dunstkalbenr") ; while in other cases 



Dropsy. 



I2g 



renal changes, perhaps the sequels of an intrauterine nephritis, are 
met which may occasion dropsies because of retention of water 
or on account of some infectious toxic influence present. 

The dropsical transudate is usually a colorless or wine-yellow 
water-like fluid, generally containing a smaller proportion of 
albumen than the lymph and fluid exudates, as a rule showing 
only o.i to 0.8 per cent, albumen, according to Perls up to 5 




Pig 3. 
Anasarca universalis congen., so-called water calf. 

per cent. (Lymph and blood plasma contain about 7 per cent.) 
The proportion of salines is the same as in the plasma (0.8 per 
cent). [The precise composition, particularly as relates to pro- 
teid, varies in the different types of dropsical fluid ; and even in 
the same subject the amount of proteid is not identical in fluid 
from different parts of the body, that from the subcutaneous 
tissue being usually marked by the lowest proteid content, while- 



130 Disturbances of Circulation. 

that from the serous cavities, especially the pleura, is apt to be 
richer in albumen.] In case of coincident escape of blood 
corpuscles (in passive hyperemia) admixture of these elements 
with the transudate may occur to a sufficient extent to give it a 
blood-red color and occasion fibrin deposition (hydrops hcemor- 
rhagicus). In other instances admixture of fat from the blood 
or from fatty degeneration of the cellular elements macerated in 
the fluid may give a milky appearance to it (hydrops adiposus, 
chyliformis) ; and in abdominal dropsy a similar appearance may 
be occasioned by rupture of the chylous vessels and admixture of 
chyle with the fluid (hydrops chylosus) . 

The amount of fluid in the large body cavities may reach con- 
siderable volume, 10, 50 to 100 liters in large domestic animals. 
Such quantities of fluid are naturally capable of exerting marked 
pressure upon the different adjacent organs, and distend the walls 
of these cavities. Consequently in case of ascites the peritoneal 
cavity is considerably enlarged and becomes a fluctuating sac ; the 
pericardial sac attains a wide outline and fluctuates ; and even the 
chest wall may be distended arid barrel-shaped from the separation 
and outward displacement of the lower ribs. In the foetus, in 
which the fontanelles are still yielding, the covering of the brain 
becomes a huge sac, partly membranous, partly made up of the 
cranial bones forced apart and transformed into thin plates. 
When the transudate fills the spaces of a tissue the porous cellular 
structure becomes a gelatinous, amber-colored, swollen mass, 
from the cut-surface of which a serous fluid drips and whose 
doughy swelling retains for a long time the pressure marks of a 
finger. Sometimes bladder-like collections or cysts may form 
from the forcible distension of the connective tissue spaces. 

Various terms have by custom been applied to these accumula- 
tions of transuded fluid. (Edema of the skin is spoken of as 
anasarca (from & v & and <rdp£, flesh; supply hydrops); collec- 
tions in the pleural cavities as hydrothorax ; in the pericardial sac, 
hydro pericardium; in the peritoneal cavity, ascites (from &<tk6s, 
belly; namely, hydrops ascites) ; in the tunica vaginalis testis, 
hydrocele (from vdufp-K-Z/Xv , water rupture) ; in the cranial cavity, 
hydrocephalus. 

The result of the oedema depends upon the location and cause 
of the condition. Local dropsies of the skin may last a long 
time, but eventually disappear after the removal of the cause 
and the resorption of the fluid. CEdema of the tissues about the 



Thrombosis. 131 

laryngeal entrance (oedema of the glottis) is dangerous, occasion- 
ing asphyxiation by narrowing the air passages ; oedema of the 
lungs and of the brain may be fatal by causing functional dis- 
turbances of these organs. The mechanical pressure effects of 
collections of fluid in the serous cavities upon the blood circula- 
tion, the compression and displacement of viscera (pressure on 
the diaphragm), as secondary results of the dropsy, increase the 
severity of the primary disease which was the cause of the dropsy 
(affections of the heart, liver or kidneys). 

Obstruction of Blood Vessels. Thrombosis and Embolism. 

Obstruction of blood vessels may be due to the formation within 
them of relatively solid plugs made up of the blood constituents, 
this process being known as thrombosis (6 0p6^os, mass; from 
rp^0w, to make firm or compact), or to forcible lodgment in their 
lumen of materials conveyed by the blood current, this latter pre cess 
being known as embolism ( ifi-p&Wciv , to throw in). 

It is well known that blood- outside the body clots in a few 
minutes after its escape from the vessels, as after venesection. 
There is formed from the blood a red jelly-like mass, the bloody 
cruor sanguinis; over the surface of which there collects a pale 
yellow fluid, the blood serum. The clot is primarily constituted 
of fibres of coagulated fibrin, which include the blood plaques. In 
case of slow coagulation the red corpuscles sink to the bottom of 
the containing vessel and thus the superior part of the coagulum is 
largely occupied by the lighter and therefore less readily sinking 
white blood corpuscles ; for which reason the surface of the clot 
shows a yellowish-white layer composed of fibrin and leucocytes, 
the so-called buffy coat. The formation of fibrin is the main fea- 
ture of extravascular coagulation, and can be directly followed in a 
drop of blood under the microscope. In a blood drop placed upon 
the cold slide the film can be observed to separate as fine threads, 
and these, with the platelets adhering, unite with each other to form 
a network (Birch-Hirschfeld). Fibrin is an albuminous substance, 
existing in solution in the circulating blood in the plasma (the 
so-called fibrinogenous material or fibrinogen), which separates as 
a coagulating calcium compound with proteid when acted upon in 
the presence of calcium salts by a ferment known as the fibrin 
ferment. 

Following the apt comparison of Birch-Hirschfeld, blood coagulation 
may be thought of qs somewhat analogous io ivnnct coagulation of milk. 



132 Disturbances of Circulation. 

In the presence of lime salts of the milk, casein (which is similarly a 
calcium proteid combination) is separated from the milk by the lab- 
ferment, leaving a serum, the whey. 

Coagulation of blood may be checked or inhibited by certain 
chemicals which destroy the ferment or which dissolve the fibrin 
immediately after it is formed (potassium citrate, or oxalate, extract 
of the cephalic glands of the leech). [Extract of the cephalic end 
of the hookworms of the dog possesses a similar property.] 
So, too, coagulation fails if the inner surfaces of the vessel in which 
the blood is caught be covered with vaseline, thus preventing adhe- 
sion (Freund). 

After death the blood clots quickly and in a manner similar to 

extravascular coagulation, especially in the heart and larger vessels ; 

in the capillaries it remains fluid for a longer time. In the presence 

of toxic substances having solvent action upon the blood and fibrin, 

too, coagulation is incomplete (hemolytic substances, as some of 

the bacterial products, presence of excessive amounts of carbon 

dioxide in the blood). Cadaveric clots are homogeneous, soft, 

elastic, gelatinous masses which look like casts of the vessels, are 

* 

without lamination, and are either of a dark red color throughout 
or of a mere or less yellowish gray to amber hue with jelly-like 
semi-transparent appearance. The latter form, comparable to the 
"buffy coat" are met in anaemic states and gradual cardiac failure, 
the blood cells in such instances settling and the fibrin containing a 
large amount of serum. [In these heart-clots the dark red homo- 
geneous examples are commonly interpreted as indicating rapid 
death and quick coagulation before the corpuscles have had time 
to separate; they are thus referred to as post-mortem clots. On 
the other hand, the yellowish translucent coagula, occurring in slow 
circulatory failure, are often spoken of as ante-mortem clots, from 
the idea that they form or start to form during the period of slow- 
ing of the current prior to death, the red cells at least sinking 
more or less from the general blood volume prior to the actual 
stoppage of the current and coagulation of the blood.] 

Coagulation and thrombus formation within the vessels of the 
living takes place from the following causes or favoring conditions : 

1. Entrance of chemicals into the circulation favoring coagula- 
tion of the blood (ferment thrombosis) : By the injection of ether 
and other chemicals, the introduction of substances destructive to 
the leucocytes, injections of emulsions of various parenchymatous 
tissues (brain, adrenals) or of the expressed juices of the thymus 



Thrombosis. 



133 



body, testicles, etc., or of laked or altered blood, it is possible to 
bring about extensive coagulation with fatal effect. Such experi- 
mental findings warrant the assumption that the occurrence of 
tiirombosis is, at times, in infections and diseases accompanied by 
tissue destruction dependent upon the coagulative action of microbic 
poisons or tissue products permitting the formation of fibrin fer- 
ment by the disintegration of leucocytes. 

2. Slowing and cessation of the blood current : It has been 




•A. 




Fig. 4. 
Cardiac valvular thrombosis (right ventrical of heart of hog). 

shown by experiment that after double ligation of a vein or artery, 
although the blood in the segment between the ligatures is entirely 
stagnant, it may remain fluid' for months (Baumgarten, Senftleben 
and others). Nevertheless in situations where blood vessels are 
expanded, particularly when the seat of pathological dilatations, and 
when the flow of the blood is slackened, thrombi are particularly 
likely to form, because these ectases favor the agglutination of 
leucocytes and plaques from which arises the inception of the 
thrombotic process {stagnation thrombosis) . 



i34 



Disturbances of Circulation. 



3. Alterations of the lining of the vascular wall : Lesions of 
the vascular intima resulting in the destruction of the endothelium 
and thus causing a loss of the natural smoothness of its surface give 
opportunity for adhesion of platelets and white blood corpuscles to 
the roughened surfaces and give origin to thrombus formation 
{adhesion thrombosis). In lacerations, incised and puncture 
wounds as well as contusions of the vessels, thrombi invariably 
form, an important feature in wounds both as regards healing and 
preservation of life, the clot formation gradually closing the 
rent in continuity of the vessel and checking the loss of blood. 
Thrombosis also takes place in case of vascular changes caused bv 
bacterial invasion, parasites, perforating neoplasms, and in vessels 
in the neighborhood of active inflammatory lesions, as upon the 
valves in case of endocarditis, in the vessels of the lungs in pneu- 




Fig. 5. 
Thrombosis in a cavernous angioma of the liver of a cow. 



monia, in parasitism of the arteries by strongylus armatus, in case 
of invasion of pyogenic bacteria in the umbilical vein, etc. 

As a rule two or three conditions favoring thrombus formation 
cooperate to cause it ; thus when a thrombus is formed after 
bacterial invasion of a vessel, it is partly the result of special 
ferment production, partly due to injury of the intima. 

The composition of thrombi varies with the rapidity of forma- 
tion and the causes of production. Those rapidly formed and 
caused by special elaboration of ferment are often quite like the 
clots of external haemorrhage, homogeneous and of a dark red color 
throughout, being made up mainly of fibrin and red blood corpuscles 
{homogeneous thrombi) ; microscopically the fibrin forms an intri- 
cate reticulum of delicate threads in a radiating or stellate form 
around the disintegrating leucocytes which furnish the fibrin fer- 
ment (coagulation centers of Al. Schmidt and Ribbert). Stratified 



Thrombosis. 135 

or layered thrombi, usually forming upon a limited area of the vessel 
wall, begin by the adhesion of white blood corpuscles and plaques 
to the altered part of the vessel wall and their accumulation at such 
site; upon this basis fibrin is deposited in layers of varying extent 
and quantity, enclosing the corpuscular elements of the blood in its 
structure. The arrangement of this coagulum is often such that 
in microscopic sections the framework of the thrombus may be 
observed to be formed of wavy trabecula of granular substance 
made up of blood platelets (Ribbert) ; these bands always sur- 
rounded by a broad zone of leucocytes and between them the net- 
work of fibrin fibrils spread out with the red corpuscles included 
in the reticulum (Ribbert). Corresponding with the greater or 
smaller amount of the constituent fibrin and cells and the types of 
formation described, the general appearance of thrombi and their 
color and consistence vary. There may be distinguished the follow- 
ing varieties from this viewpoint: 

1. Red thrombi, showing a homogeneous, blood red, gelatinous 
mass, similar to the post-mortem clots ["currant- jelly thrombi"]. 

1. White and grayish-red thrombi, reminding one of bacon- fat 
or spinal-cord tissue or minced meat, not transparent, but opaque, 
dull, of the consistence of soft rubber or cooked minced meat. 

3. Mixed and stratified thrombi, made up of alternating layers 
of red and white coagulum, well seen in cross-section, often arranged 
concentrically like the tunics of an onion and separable like the 
leaves of a book from each other. The reason for this lamination 
and alternating arrangement is to be found in the fact that new 
layers are not being continuously formed upon the primary clot 
but are deposited at intervals, the older layers thus attaining a cer- 
tain degree of firmness, and the new ones not adhering so closely 
to the previously formed strata and remaining easily separable from 
them. Where such mode of increment is frequently repeated the 
thrombus may exhibit quite a number of layers. The surface of 
these thrombi may be either smooth or uneven, often marked by 
ridges or ribs ; the latter peculiarity is due to the trabecula of blood 
platelets and leucocytes extending to the surface and forming ledge- 
like projections with trough-like depressions between them (similar 
to the wavy deposit of river sand, and according to Zahn probably 
produced by the wave-like motion of the blood). [Such appearance 
may be produced, too, by the uneven contraction of the mass, the 
shrinkage being most marked in the fibrinous network lying between 
the coarser plaque-trabecula.] 



136 Disturbances of Circulation, 

The clots appearing at the beginning of thrombosis are known 
as primary (autochthonous) thrombi; the coagula subsequently 
deposited upon them as secondary or consecutive thrombi. The 
former are more or less firmly attached to the vessel wall (parietal 
thrombi) ; the latter usually lie free in the lumen as cylindrical 
plugs with conical or rounded ends. The thrombus increases' prin- 
cipally in the direction of the blood stream, in the arteries toward 
the periphery of the circulation, in the veiris centripetally. The 
length may be quite considerable, as' in those extending from the 
veins in the neck down into the heart, or from the aorta at the 
level of the renal artery down into the arteries of the popliteal space 
and leg with or without (discontinuous) continuity. The thickness 
depends upon the calibre of the blood vessel ; parietal clots are at 
first flat, marked with wavy ridges, villous, or in the pockets of- the 
valves of the veins may form smoothly rounded plugs (valvular 
thrombi) ; with growth the thrombus may cause complete occlusion 
of the vascular lumen (total occluding thrombi). In arteries 
thrombi are usually smaller than the calibre of the relaxed vessel, 
being compressed by the contraction of the pulsating vessel wall. 
In aneurisms and in the cardiac chambers there occur huge irregular 
nodulated thrombi, sometimes are large as the fist. Thrombi in 
the course of time undergo a number of changes (metamorphoses) 
as well might be supposed. They are but dead masses made up of 
coagulated and necrotic elements and may shrink, becoming firmer, 
drier and smaller ; such changes depending upon changes in the 
structure with homogenization of the fibrin and plaques and upon 
pressure exerted by the walls of the vessels. In clots which have 
undergone such changes there may occasionally take place a calcare- 
ous deposit (vein stones, phleboliths). As a result of such shrink- 
age the vascular lumen may again become partially permeable to the 
blood. [The diminution in size of an old clot depends in an im- 
portant degree upon the shrinkage of its own fibrinous network ; 
this may be easily noted in the shrinkage which takes place in any 
clot outside the body, with the separation of the serum originally 
present in the coagulum, the question of compression by the vessel 
walls being in such case entirely eliminated.] The most common 
change consists in a softening of the thrombus, the clot being trans- 
formed by fatty degeneration of its leucocytes [and liquefaction of 
any of its elements] into a gray or grayisli-red mass of pultaceous 
consistence somewhat like minced meat. This change may be a 
favoring circumstance, but is open to serious consequences. In 



Thrombosis. 



137 



case the substance is broken up into a finely granular fatty material 
this may be taken up by the blood current and washed away and 
the lumen of the vessel may thus be 
again established, or through the soft- 
ened clot the blood stream may some- 
times force one or more passageways 
(canalization of the thrombus). 
Should, however, larger fragments, 
as a result of the degenerative 
changes, be loosened from the coagu- 
lum and swept onward by the current 
of blood they may find lodgment in 
some other part of the circulatory ap- 
paratus and give rise to embolism. 

A thrombus acts as a foreign 
body upon the living vessel walls 
with which it is in contact ; and its 
characteristic properties excite an in- 
vasion by leucocytes and phagocytic 
activity. The latter may, as is uni- 
formly true in case of small traumatic 
thrombi, bring about complete ab- 
sorption of the clot, Coincidently 
there is established an inflammation 
of the vessel wall with fibroplastic 
and angioplastic proliferation, result- a 
ing in the formation of embryonic 
connective tissue and vascular buds 
from the endothelium and vasa vaso- 
rum and their penetration into the 
thrombus. These proliferating ele- 
ments replace in time more or less 
completely the clot substance. In 
case the thrombus were a parietal 
one, occupying only one side of the 
vessel wall, as after venesection, after 
removal of the clot the connective 
tissue contracts and shrinks into a 
flat scar or mere thickening of the 
wall. Where the thrombus occupies the whole lumen the 
embryonic tissue develops about il, and in its growth pene- 




Fig. 6. 

Schematic section of a throm- 
i>ost>ii vein; somewhat en- 
larged, i After Thoma. 1 



1 3 8 



Disturbances of Circulation. 



trates the mass ; and in the site of the clot there is formed a 
mass of connective tissue. These changes are known under the 
term organization of the thrombus. The vessel in the situation in 
question is converted into a solid cord, its lumen completely 
obliterated; and as a result of shrinkage of the newly formed con- 
nective tissue the part eventually may be seen as a thin string-like 
obliterated section of the vascular tube. Now and again spaces 




Fig. 7. 

Embolism of branches of the pulmonary artery ; the superior embolus almost com- 
pletely adhering to the vessel walls and shrunken. Somewhat reduced. 
(After Thoma.) 

are left in the connective tissue, however, through which blood in 
some degree may pass. 

If a thrombus or a portion of a thrombus should break away, it 
is carried forward with the blood current and must find lodgment 
at some point where the calibre of the artery is less than the diam- 
eter of the floating mass. The latter is then spoken of as an 
embolus, and the process as embolism. Detachment is especially 
likely to take place in connection with softening of a thrombus, in 
which process the clot may easily crumble ; however, even entire 



Embolism. 139 

thrombi, no matter whether loosely or firmly attached, may some- 
times accidentally be torn loose by external force exerted upon the 
vessel through movements occasioning twisting of the vessels or 
increase of blood pressure. At the points of branching of the 
vascular tubes it may happen that a thrombus or embolus may 
strike upon the dividing angle and here again be broken into frag- 
ments or may remain fixed at the point of division. It is quite 
likely that an unusually long, flexible and tough thrombus may so 
lodge at these places of division as. to extend into both branches 
of the vessel, riding as if in a saddle (riding embolus). A long 
cylindrical, flexible thrombus may, moreover, be thrown into folds, 
twisted in serpentine fashion and compressed into a mass by the 
force of the blood stream. 

Although an embolus displaced from its original site is forced 
into a relatively narrow portion of the vessel, it does not neces- 
sarily at once completely occlude the lumen, since as a broken 
fragment of a thrombus it need not retain the cylindrical shape 
of the vascular tube, but may well be of irregular and angular 
outline. . Such emboli, particularly when of the riding type, are 
apt to leave room free about them for the passage of blood. Cyl- 
indrical or round emboli are comparatively easily forced into the 
vascular lumen and give rise to complete obstruction. An embolus 
which has become lodged tends to further enlargement, either by 
the massive coagulation of the stagnant column of blood adjacent 
or by the deposition of thrombotic layers. Sooner or later this 
leads to complete obstruction of the vessel. In these cases it is 
often difficult to determine whether there was primary thrombosis 
or whether an embolism formed the nucleus of the blood clot, 
which, from the formation of new layers, comes to completely fill 
out the lumen of the vessel, and the original embolus may, more- 
over, have been very small, and entirely hidden by the further 
depositions. 

The course traversed by an embolus is determined by cir- 
culatory circumstances. An embolus carried from the veins must 
always pass into the right heart and thence into the pulmonary 
arteries ; it may, however, adhere to the auriculo-ventricular valve 
leaflets in the heart. Its convection to the heart is easy, the veins 
becoming wider and wider from the periphery centrally to the 
venae cava?. If therefore a fragment become loosened from a 
thrombus in veins of the foot, thyroid, uterus or liver it would 
be swept by a continually widening current to the heart. Coming 



140 



Disturbances of Circulation. 



from the intestine, stomach or spleen in the portal vein, emboli 
must lodge in the liver ; embolism of the latter organ arising also 
from the umbilical vein, inasmuch as there is no direct communica- 






Aorta 



Niere 




%Mer\ I «*« 



Fig. 8. 

Schematic representation of the circulation with fragments of thrombi at different 
positions (cf. text). Lungencapillaren, pulmonary capillaries; Linke Herzk., 
left cardiac ventricle : Rechte Herzkammer. right cardiac ventricle : Magen, 
stomach ; Milz, spleen ; Darm, intestine ; Nabel, umbilicus ; Leber, liver : Niere, 
kidney. 



Embolism. 



141 



tion of the portal and umbilical veins with the vena cava, their 
blood passing into the fine meshed capillary network of the portal 
vein within the liver substance. (In calves, however, where the 
ductus Arantii forms a direct passage between the umbilical vein 
and the vena cava the lung may stand equal chance of embolism 



Art 

haemorrhof\ { 
dalisi 



Einige 
"dilnndarmdste 



.coeci 




Fig. 9. 

Thrombosis of the colic arteries of a horse; a riding embolus in arteria ececi. 
Vordere Gekroswurzel, anterior mesenteric trunk; einige diinndarmaste, 
branches to small intestine. 

from the last named source.) Emboli from the left heart, from the 
lungs (pulmonary veins), entering the aorta and arterial tree always 
find their way into the peripheral arterial branches, as from the 
anterior portion of the aorta into the brain, from the posterior 
aorta into the kidneys, pelvic arteries, etc., from the mesenteric 
trunk into the arteries of the intestines. As a rule blood clots are 



142 Disturbances of Circulation. 

not so minute that they can be carried from the arteries through 
the capillaries into the veins, for which reason such emboli from 
the pulmonary arteries become fixed in their branches, that is, in 
the lungs ; other types of emboli, however, as minute animal 
parasites or bacteria, may traverse a capillary area and may there- 
fore pass from the greater into the lesser circulation and in turn 
arrive again in the greater. 

In very rare instances in human beings, where there is a patulous 
foramen ovale, emboli have been encountered in the aorta and its branches 
which did not originate in the left heart or lungs, but which passed 
directly from the right into the left heart through the patulous opening. 
When first seen, before the condition of the foramen ovale has been 
noticed, the existence of such embolism seems inexplicable and confusing, 
for which reason such an occurrence is spoken of as paradoxical embolism. 
In addition, it should be mentioned that there is a possibility of retrograde 
embolism of embolic substances in the veins. This, according to Ribbert, 
may be explained on the supposition that clots or emboli of any type 
which happen to lie close to the inner surface of a comparatively large 
vein are always subject to slight backward repression by recurrent waves 
of the venous blood (venous pulsation in passive congestion), somewhat 
as at the shore the surging wave carries back with it a floating log into 
the sea. If the venous current to the heart be weak^ as in congestive 
states, it may not carry the embolus forward with it, while the more 
powerful backward impulse forces it gradually back toward the periphery 
to the capillaries. [This is well seen sometimes in cases of valvular 
insufficiency and regurgitation.] 

The results of thrombosis and embolism vary with the vascular 
conditions, the size and nature of the obstructive substance and the 
relative importance of the affected organ. In part they are purely 
mechanical, depending upon the degree of narrowing or obstruction 
of the lumen occasioned by the process and the consequent dis- 
turbance of circulation ; in part the results may be specific (pe- 
culiar), the nature of the thrombus involving some special prop- 
erties (as pyogenic or putrefactive agencies, or tumor forming 
elements). Thrombosis of arteries occasions primarily an anaemia 
of the organ or area supplied by the artery affected. This an.xmia 
in vital organs like the brain or heart or lungs necessarily imme- 
diately induces disturbances of function dangerous to life itself 
(fainting, cessation of cardiac action, phenomena of asphyxia), if 
an important artery be involved and quick compensation by anasto- 
motic blood supply is impossible. In case, however, branches of 
the occluded or obstructed artery are so connected with other 
adjacent arteries that a sufficient amount of blood is supplied to 



Embolism. 



143 



the organ by these anastomoses or collateral communications, the 
anaemia is likely to be only of short duration and without func- 
tional disturbance. In many organs such collateral paths are very 
abundant, and in some, as in the muscles and lungs, they are so 
numerous and of such calibre that sufficient blood is transmitted to 
the blocked area of the artery by the ordinary collateral circula- 
tion without any special effect. The blood which previously tra- 




Fig. 10. 

Femoral artery of a large dog, injected 
three months after ligation. (After 
Porta.) 



Fig. 11. 

Carotid artery of 
a goat, injected 
thirty-five months 
a f t e r ligation. 
(After Torta.) 



versed the occluded vessel is of course distributed throughout the 
permeable branches arising proximal to the site of obstruction 
and driven into these by the arterial pressure. The blood pressure 
in these collateral paths must therefore be somewhat raised, for 
which reason, as well as from the probability that the anaemic area 
actually sucks in the blood from these paths, the blood in the 
collaterals flows with increased rapidity. This excess of pressure 
also determines an additional dilatation of the collateral vessels, 



144 



Disturbances of Circulation. 



corresponding at first merely to their extensibility ; but after the 
dilatation has persisted for a time there also occurs a proliferation 
of the. cells of the vessel walls in consequence of the altered con- 
ditions of tension, not only causing narrow arteries to assume 
wide calibre, but changing capillary vessels into arteries. It is 
in this manner that a tissue whose principal artery has been ligated 
or occluded by thrombosis has its blood supply restored. The 
development of collateral circulation, however, requires time before 
complete compensation is attained; and should the existing anasto- 




Fig. 12. 

Embolism of an artery with congestion of 
its two vense comites. 



Fig. 13. 
Supply by anastomotic channels. 



::zr> 



motic channels be very small, few or entirely absent, the tissue must 
in the interim suffer from the circulatory loss, be more or less com- 
pletely deprived of its nutriment and perish. This is particularly 
true when there are absolutely no arterial anastomoses. Arteries 
which possess no communicating channels with neighboring arterial 
areas are commonly known as end-arteries, following Cohnheim. 
Parts of organs supplied with no arterial anastomoses have of 
course capillary communications with the adjacent tissues, but the 
small amount of blood which passes through these minute channels 
is often insufficient to maintain the nutrition of the area deprived 
of its arterial supply ; only in case of very small areas is the 



Infarction. 145 

capillary supply sufficient for this purpose. Moreover it may hap- 
pen that it is not one single artery that is blocked, but that at the 
same time its anastomosing vessels are also occluded, under which 
circumstances there necessarily result circulatory disturbances hav- 
ing serious consequences. The area which is deprived of its blood 
supply loses its blood color, and assumes a paler and drier appear- 
ance than the' surrounding tissue; the blood remaining in it be- 
coming decolorized because its haemoglobin is dissolved, disin- 
tegrated or dispersed by diffusion, and the anaemic tissue, in which, 
too, the lymph is stagnant and coagulates, undergoing regressive 
metamorphoses. Such an anaemic and dead area is known as an 
anemic infarct. 

A tissue which is thus cut out of the circulation and 
deprived of its arterial blood supply is not necessarily anaemic 
but on the contrary may be the scat of a distinctly pathological 
engorgement as a result of regurgitation of blood from the veins. 
Particularly where the veins of the part whose arterial supply 
has been occluded anastomose with adjacent veins, the blood, which 
in the latter vessels is under a certain amount of pressure, flows 
ovetf into the former and back into the anaemic network of capil- 
laries ; just as the water from a brook moves back into the side 
ditches of a stream if these have no fall. There is no force from 
the arteries in such a site capable of driving the blood through the 
affected area and the capillaries in which the venous blood collects 
become distended and their walls flaccid and permeable from the 
lack of normal bathing with flowing blood. The venous blood 
thus stagnating in the capillaries partly leaks through their walls, 
partly undergoes coagulation ; and the whole area thus engorged 
with blood assumes a dark red hue. Such an area is spoken of as 
a hemorrhagic infarct {infarcire, to stop up). [Others would 
refuse the importance attached by the author to the above idea of 
a venous regurgitation giving rise to the engorgement of the in- 
farcted area with blood. Anastomotic communications are usu- 
ally more numerous and free between veins than between arteries ; 
and if this be true and the author's views correct, anaemic infarcts 
should be the exception rather than of as common occurrence as 
they actually appear. If venous reflux were as easy as supposed 
by the older adherents of this theory, anaemic infarcts should be 
practically unknown. From the editor's viewpoint the process is 
more easily understood if we accept the belief, which seems rea- 
sonable, that there are no true end-arteries and thai there arc al- 



146 Disturbances of Circulation. 

ways some small anastomotic channels between adjacent terminal 
arterial areas. Through such anastomoses, inappreciable under 
normal conditions but distended by the collateral rise of blood 
pressure when the embolism diverts the blood into the surround- 
ing areas of distribution, the blood enters the infarct. The ques- 
tion whether in any given case an embolism should cause an anaemic 
or a haemorrhagic type of infarct is largely determined by the 
texture of the tissue in which the lesion occurs, anaemic infarcts 
being met in relatively firm tissues as in the kidneys, and haemor- 
rhagic in looser structures as in the lungs. The explanation of 
such distribution is not entirely clear but probably rests in the 
facility afforded by the tissues at the border of the infarct for dis- 
tension of the capillary anastomotic channels entering the infarcted 
area. Naturally the looser the texture, the greater the ease of 
such dilatation. It should however be realized that the collateral 
congestion existing along the border of the infarct is productive of 
swelling and of pressure upon the periphery of the infarct. 
Granted a fairly firm structure, such pressure should compress the 
very channels of ingress into the interior of the infarct which are 
here supposed to give opportunity for the entrance of blood ; and 
in such instances the part occluded should remain anaemic. If, 
however, the tissue be loose in texture such compression cannot be 
of sufficient importance to occasion the interference with these 
anastomotic channels just suggested; and here the blood may by 
such paths enter the area from the zone of collateral hyperaemia 
and give rise to the appearance of a haemorrhagic infarct. In- 
farcts of the lung are usually haemorrhagic in type in conformity 
with the natural looseness of this tissue ; but the writer recalls 
a recent case of an anaemic infarct of a collapsed lung, bear- 
ing out the above theory. There is no objection to the author's 
views in so far as entrance of blood to the infarct through venous 
anastomoses may constitute a part of the process ; but to the 
writer's mind it is excessive to suppose that this factor with reflux 
of blood into and through the venules and capillaries from the 
veins is the sole explanation of the phenomenon ; and in his opinion 
both arterial and venous anastomoses may contribute, regulated 
however by the factors of border swelling, texture of tissue and 
pressure, to determine to what degree the entrance of blood may 
be possible] . 

Microscopically a haemorrhagic infarct exhibits the capillaries of 
the part turgid with blood and the lymph spaces and all the tissues 



Infarction. 



147 



infiltrated with hemorrhagic effusion. In large infarcts the con- 
gestive reflux of venous blood is often restricted to the periphery 
of the area alone, the central portions remaining anaemic and hav- 
ing therefore only a red areola. 

Infarcts as a rule are conical in shape, the apex of the cone 
at the position of arterial occlusion, the expansion from this point 
corresponding with the branching of the artery. From fusion of 
closely situated infarcts or in those of flat organs like the wall of 
the intestinal canal, the conical shape may be indefinite and the 
outlines suggestive of a map. Hemorrhagic as well as anaemic in- 
farcts occasion destruction of the tissue, the circulation being en- 




Fig-. 14. 
Conical hemorrhagic infarcts in a portion of the kidney of a cow. 

tirely ended in the area involved ; the tissue with all the blood which 
has engorged it being reduced to a mass of coagulated necrotic ma- 
terial. Such an area excites an inflammation in the surrounding 
tissue, to the formation of an actual inflammatory zone of demarca- 
tion ; a wall of leucocytes collecting around the area of coagulated 
material, fibroblastic and angioplastic cells from the surrounding 
healthy structure penetrating the infarct, whether it be anaemic or 
hemorrhagic, the blood and disintegrating tissue of the infarct 
being removed by phagocytosis, and the site of the infarct being 
eventually occupied by a mass of contracting connective tissue 
(infarct scar). Such cicatrices are quite common in the kidneys 
(cicatricial kidneys). When cither an anaemic or hemorrhagic 
infarct is related to some surface infected with bacteria, these in- 



148 



Disturbances of Circulation. 



variably invade every part of its tissue, causing its destruction by 
moist gangrene, as is regularly seen in such lesions of the in- 
testine (septic destruction of the intestine). 

Thrombi, developing in the veins so as to cause their occlusion, 
of necessity interfere with the passage of the venous blood from 
the periphery, and of course give rise to passive congestion. The 
duration and termination of such cases also depend upon the 
presence or absence of proper collateral communications. In case 
of a partial or complete occlusion of unpaired venous trunks (vena 




Fig. 15. 

Cicatricial shrinkage after embolism (hemorrhagic infarcts) of the kidney 

of a hog. 



cava, portal vein) or in case of synchronous thrombosis of a num- 
ber of venous tributaries (veins of the lung) a serious passive con- 
gestion is occasioned, with stasis of the blood column, hemorrhagic 
infiltrations or congestive transudations. Should there be a num- 
ber of collateral branches of sufficient calibre the stagnation of 
Wood will extend from the point of occlusion only to the first 
collateral branch, and the blood will pass without difficulty by the 
collateral route to the heart ; should the anastomotic passageways 
be narrow they may become dilated by the pressure of the ob- 
structed blood and the tissue be gradually relieved of its congestion, 
provided the degree of dilatation will accommodate the blood ac- 
cumulated in the various venous channels of the structure. Very 
small veins and the capillaries everywhere in the part may be so 
distended as to serve the purposes of drainage, thus conducting 



Embolism. 149 

the blood by a round-about way into one of the venae cavae. Clots 
and fragments of clots from the capillaries and veins pass as 
emboli to the right heart and thence to the lungs. 

In the same way as clots, a variety of substances may, if once 
they have gained entrance to the blood, be carried along by the 
current and give rise to embolism. Virchow and Cohnheim, whose 
studies were fundamental to our knowledge of the embolic process, 
showed that small balls of wax introduced into the blood vessels 
are carried along by the current, lodge in some relatively narrower 
place in the vascular tube, and give rise to all the mechanical con- 
sequences of embolism. Sometimes parasitic worms which have 
succeeded in making their way from the intestine into the radicles 
of the portal vein are conveyed with the portal blood into the liver 
and may be carried thence onward as emboli to the heart and lungs ; 
very minute animal parasites, as the rounded oncospheres, measur- 
ing only 20 to 40 micromillimeters in diameter, and larval trichinae, 
may slip through the capillaries of the pulmonary circulation, often 
measuring 0.1 mm. in diameter, and thus gaining access to the 
arterial stream be carried to any of the organs. It may be easily 
appreciated from this why the liver and lungs are the most 
common sites for echinococcus cysts ; and the embolic mode of dis- 
tribution of the parasites is recognized from their usual wide dis- 
semination throughout the whole organ. Of the larger parasites 
which the blood may aid in distributing, liver flukes deserve special 
mention ; these sometimes in their migrations in the hepatic par- 
enchyma penetrate into the branches of the hepatic vein and may 
pass with the blood through the right heart into the lungs. The 
mechanical consequences of embolism by these animal parasites are 
usually of little importance because of the minute size of the bodies 
and the relative certainty of sufficient anastomotic supply to the 
small areas affected ; and disturbances are only occasioned by 
pressure, etc., in case the invading parasite increases in size. The 
larger parasites like strongylus armatus are capable of directly 
causing the same mechanical effects as described in connection 
with blood clots (as cerebral embolism with infarction). 

The entrance of air and of droplets of fluid fat may also oc- 
casion circulatory disturbances in a purely mechanical manner, in 
the same way as blood clots. Air embolism is of rare occurence 
and is met with in operations on the neck.* The air which is 
drawn by the suction force of the heart through a valvular venesec- 

*Traumat!e aortpmla was Mrs! observed in. the horse by the French veterin- 
arian, Verrler (1806). 



150 Disturbances of Circulation. 

tion wound into the jugular vein, or which is accidentally intro- 
duced in intravenous injection, becomes mixed with the blood in 
the form of bubbles of various sizes. In case of healthy animals 
with normal blood pressure, moderately large quantities of air (5 
to 10 cubic centimeters in dogs, sheep, horses) injected into the 
jugular vein are sometimes born without harmful results, the air 
disappearing quite rapidly by absorption in the circulating blood. 
In animals with low pressure and a tendency to accumulation in 
the right heart (as after operations and after loss of blood in 
parturition) the air bubbles are apt to accumulate in the right 
heart and form a large elastic air cushion which is not forced 
onward by systole, being only compressed by cardiac contraction 
and expanding again in diastole. In consequence the blood is 
dammed back in the right heart, and there results a marked dilata- 
tion of the right ventricle, reaching two or three times its normal 
volume. (Death takes place from the cardiac dilatation and suf- 
focation, the blood being prevented access to the lungs. Accord- 
ing to Francois Franck it may also be possible that some of the 
air passes through the lungs, and. traversing the left heart into 
the coronary arteries, brings about embolic occlusion of the latter 
and anaemia of the myocardium.*) 

Fat embolism is usually met in connection with severe con- 
cussive lesions of the bone marrow (Ribbert). The occurrence of 
fracture of a bone with such concussion allows lacerations of the 
delicate walls of the venous capillaries to take place, after which 
fat droplets from the fat cells abundantly present in the marrow 
may pass into the blood (Ribbert). Access of fat into the blood 
may also be thought possible from the liver cells in case of con- 
tusion of this organ, its cells also being usually rich in fat (Rib- 
bert). The oil droplets are first carried with the venous blood to 
the lung, where they lodge in the small arteries and capillaries, 
the capillary network often appearing turgid as if filled with a 
fatty injection mass. From the occlusion thus brought about 
haemorrhagic infarcts are formed in the lungs, usually a transient 
condition (may be proved by injecting a fat emulsion into the 
jugular). The liquid fat may. however, pass through the pulmon- 
ary capillaries and be carried on into the left heart, whence it may 
be conveyed with the aortic blood into the cardiac musculature 
(coronary arteries), the renal glomeruli, or the brain and other 
organs. The fat lodged in the coronary arteries, just as any other 

*Recueil veter. 1903, p. 370. 



Metastasis, 



i^i 



emboli, occasions anaemic degeneration of the myocardium ; in the 
brain numerous small haemorrhages ; and in such or other analogous 
manner fat embolism may prove fatal. 

Sometimes after traumatic lesions of the tissues, cells are simi- 
larly swept into the blood, as giant cells from the marrow or liver 
cells, and lodge in the pulmonary capillaries because of their size. 
This type of cellular embolism occasions no special disturbance, the 
occlusive lesion being at the most a minute one and the cells soon 
broken up or removed by phagocytosis. However, the entrance of 
tumor cells or pathogenic bacteria into the blood, and the embolic 
transmission of such bodies, are of much more importance. Their 
mechanical effects in causing complete or partial occlusion of the 




Fig. 16. 



Pat embolism of the lum 



eight days after fracture of the leg. Drawn by 

Dr. Ziesing; X 250. 

The capillary network of the alveolus to the right is choked with blood, the 

lower one with fat and the artery likewise Just above the latter arc two 

air bubbles (showing as dark rings) and several droplets of fat which have 

escaped from it (with simple dark outline). (After Perls.) 



vessels are of minor significance because of their minute size ; but 
because of their nature they induce specific changes, the process 
being known as one of malignant embolism or as metastasis (^rdo-rao-is, 
displacement). We have here to deal with substances which have 
already given rise to pathological processes in some part of the 
system, and which are now, by being transported by the blood into 
new situations in the body, inducing the same disturbances in the 
latter. Emboli composed of tumor cells originate from autoblas- 



152 Disturbances of Circulation. 

tomata (neoplasms, tumors) whose cells in the growth of the 
mass are penetrating the walls of the blood vessels and, picked up 
6y the blood flowing by, are carried along with the stream. Wher- 
ever they lodge a new autoblastic growth develops from the multi- 
plication of the displaced cells, which retain their power of growth. 
Since usually it is not one single cell which is thus swept from the 
primary site, but whole groups of cells being loosened and 
separated from each other in the circulating blood and scattered 
throughout the capillary network of the organ into which they are 
carried, the latter becomes riddled with tumor nodules (disseminated 
or multiple embolism). In dogs, for example, which are suffer- 
ing from cancer of the thyroid gland the lungs are as a rule occu- 
pied by great numbers of nodules of the same carcinomatous char- 
acter, the cells having penetrated from the cancerous alveoli of the 
gland into the thyroid veins and having of course been carried into 
the lungs. In the same way from cancers of the mammary glands, 
the skin, the nose, etc., after invasion of the tributaries of the vena 
cava, metastatic nodules develop in the lungs. Intestinal, gastric 
and pancreatic cancers give rise to metastatic embolism in the liver, 
the tumor cells primarily gaining access to the portal vein ; only in 
case they pass through this organ does the lung become involved 
by the tumor cells. [This is true in a general sense provided the 
hsemic route is followed in metastasis. It should be added however 
that these cells may find their way by the lymph stream through 
the thoracic duct to the lungs, the liver being entirely escaped. So, 
too, it is possible by the minor anastomotic communications be- 
tween the portal system and the general venous system, as by way 
of the veins of the smaller gastric curvature, lower oesophageal 
and azygos veins, that the cells may be conveyed to the lungs 
directly, the liver being evaded.] 

Malignant bacterial embolism is determined by the en- 
trance of pathogenic bacteria into the blood vessels, quite com- 
monly the pyogenic organisms ; more rarely the vegetable organ- 
isms like the spores of moulds enter into consideration. Such 
germs may gain entrance into the circulating blood through lesions 
of the skin or mucous membranes. Lesions which were practically 
imperceptible may serve as the point of entrance [it is also claimed 
by a number of persons that in a limited degree bacteria may pass, 
as it were be absorbed, through delicate mucous membranes with- 
out the actual existence of any structural disturbance of the mem- 
brane, as Ravenel has pointed out in case of tubercle bacilli passing 
through the normal intestinal wall to the mesenteric glands], 



Metastasis. 153 

the bacteria first multiplying at this point of invasion and then 
either by way of the lymph passages, conveyed to the blood, 
or directly growing through or actively penetrating the deli- 
cate walls of the capillaries. Some bacteria are motile and are 
able to actively progress because of this property, or because of 
their minute size may be passively conveyed through the lymph 
spaces. Generally at the point of entrance the local action of the 
bacteria causes a focus of « destruction varying in type with the 
form of bacteria present, as a suppurative liquefaction or ichorous 
softening (furuncle, suppurative wounds of the skin) ; coincidently 
the destruction of the walls of the capillaries and veins permits 
the bacteria to gain access to the blood and circulate with it and 
to be carried to the heart and lung or from the intestine to the 
liver. Bacteria, too, because of their minute size may traverse 
capillary areas and therefore often pass from the lesser to the 
general circulation and become scattered widely throughout the 
system. In a strict sense they should be regarded as emboli, al- 
though primarily because of their minuteness they occasion no me- 
chanical disturbances but remain suspended here and there in the 
vascular tubes, as at places where the blood current is temporarily 
hindered (a joint) or where there are inequalities in the intima 
(valves, sharp bends in the capillaries, renal glomeruli). At such 
sites they induce the same type of changes as at the point of en- 
trance, causing inflammatory reaction, suppuration, etc., and multi- 
plying at first to the production of a definite metastatic focus and 
later making their mechanical obstructive effects appreciable when 
they have developed into masses and clumps. In other cases the bac- 
teria may from the first be disseminated in the blood in small clumps, 
or as is usually the case they may adhere to bits of thrombi which 
have been broken loose. Under such circumstances mechanical 
occlusion and specific action are to be expected coincidently or in 
close succession. Precisely as in case of simple embolism a smaller 
or larger infarction is produced and within the tissue of the 
infarct, filled up with coagulated blood and necrosed, the bacteria 
may multiply to great numbers, transforming the infarct, accord- 
ing to the specific properties of the bacteria of the embolus, into a 
suppurating focus or breaking it down into an ichorous mass. 

The most common example of malignant embolism is met with 
in umbilical phlebitis, frequently scon in newly born animals. In 
case after section of the umbilical cord, dirt infected with bacteria 
(from dung, pus, dust from the straw of the animal's bed, the 




154 Disturbances of Circulation. 

coating of the tongue of the mother animal as she licks her 
young) comes in contact with the umbilical wound, germs capable 
of causing inflammation may penetrate into the umbilical vein 
(motile bacteria). These microorganisms rapidly multiply in the 
clotted blood which occupies the vein, penetrating it possibly up to 
the liver where the portal and umbilical veins unite. Thence by 
the portal current particles of the softened and infected blood clot 

are swept into the substance of 
-'" -----^ the liver and give rise there to 

multiple abscess formation. Iso- 
lated bacteria or small clumps 
of the germs are carried on- 
ward from the liver through 
the hepatic venules (in calves 
perhaps directly by way of the 
ductus Arantii) entering the 
heart and lungs with the blood 

i of the vena cava, with prodUC- 
ite. . ^ „ v | ' *■ 

tion of further suppurative me- 
Fig. 17. . rtr 

Malignant hemorrhagic infarct of the tastases in the latter. They may 
th2 S cen f tre i . h ° rse ' suppurating ' in moreover gain access to the 

general circulation (pulmonary 
veins, left heart, aorta), as the result of which extensive pyogenic 
foci of inflammation of hsemotogenous embolic origin are produced 
widely through the body, as in the kidneys, joints, eyes or brain. 
Another striking example of embolic metastasis is seen in case of 
tuberculosis, where the tubercle bacilli may be disseminated as 
above (cf. chapter on tuberculosis). 

Lymphatic Thrombosis and Lymphogenous Embolism. The lymph 
flowing through the lymph vessels, the onward movement of which 
depends partly upon the pressure with which the fluid transudes 
through the capillaries, partly upon the compression upon the 
canals (just as a sponge is squeezed) by the movements and con- 
tractions of the organs, is also subject to coagulation. For the 
most part lymph coagulation is caused by the enzymes of in- 
fectious toxine-producing organisms and by lesions of the lymph- 
vessels with adhesion of necrosing leucocytes and separation of 
fibrin in the spaces. The lymph canals filled with lymph coagula 
are to be seen as broad strands occupied by the coagulated ma- 
terial, transparent and jelly-like, as in the interstices of the lung 
in croupous pneumonia, and strikingly shown, too, in cutaneous 



Lymphatic Thrombosis and Embolism. 155 

lymphangitis. Because of the rich and intricate anastomosis of 
the lymphatics the escape of any excess of lymph is easy by the 
collateral paths, and usually the obstruction is in time removed 
by a fatty degeneration of the clot. Commonly the lymph stasis 
therefore, is but a transient feature. Extensive lymph thrombosis 
may however lead to a necrosis of the part involved, from failure 
of removal of its metabolic products and the stagnation of the 
lymph. Fragments of the thrombi loosened and carried away 
give rise to little of pathological importance, because of the rich 
collateral communication and the fact that the paths lead into the 
lymphatic glands, as well as because of the fine or molecular dis- 
integration of the coagulated material. Only in case of the 
lymphatics of the mammary gland is there to be apprehended a 
direct passage of such material into the blood with consequent 
pulmonary embolism. 

The lymph channels are important routes of transportation of 
specific types of emboli, as tumor cells and bacteria as well as for 
the convection of all sorts of material arising from the disintegra- 
tion of tissues, dust particles, pigment, and any other minute solid 
elements. Such substances are carried along, in part free in the 
lymphplasm with its slow current, partly in the motile wandering 
lymph corpuscles which load themselves with small particles ; the 
pathological significance of their convection varying with the char- 
acter of these bodies. Thus by the removal of disintegrated ma- 
terial, cellular fragments or dead bacteria, a tissue or organ may 
be restored to its proper functional capacity, a sort of street-clean- 
ing being accomplished ; but on the other hand the convection of 
toxic matter, of cells or microbes capable of multiplication, serves 
to establish more local points (or generalization) of the disease. A 
few examples may render this more clear. In case of hemorrhagic 
extravasations, as after the fracture of a bone, the entire hemor- 
rhagic focus gradually disappears, the disintegrating blood corpus- 
cles being taken up by the lymph corpuscles wandering about and 
carried to the lymph glands for further destruction (as a result 
of which the lymph glands in the neighborhood of such hemor- 
rhagic areas become the seat of a rusty brown discoloration). 
Carbonaceous particles inhaled and lodged in the lung arc carried 
along the lymph passages to the bronchial lymph nodes, coloring 
them black. Virulent streptococci which have gained entrance to 
the mouth and pharynx are taken up by leucocytes wandering out 
and in the mucous lining, carried primarily to the pharyngeal 



156 Disturbances of the Blood. 

lymphglands, where they may perhaps multiply and give rise to 
suppuration ; thence they may travel from one lymph node to 
another (retropharyngeal, cervical, thoracic), in each setting up 
new foci of suppuration, until they finally reach the blood and pro- 
duce pyaemia. 

No matter how minute the lesion of the skin or mucous mem- 
brane, infectious bacteria may from some source gain access to 
the lymphatic radicles and occasion their specific processes in the 
lymph channels and at their points of deposit in the lymph glands 
(cf. tuberculosis and carcinoma). Lymphogenous extension or 
embolism is therefore to be regarded as an important factor in the 
generalization of local infectious processes. 

Pathological Changes of the Blood. 

The blood supplies the tissues with the oxygen essential to their 
life, besides the albuminates, carbohydrates and water; it removes 
their metabolic products and is the principal factor in the distribu- 
tion of heat; it, therefore, maintains the functions of the nervous 
system, the heart and all of the organs as their liquid nutrient, their 
source of heat and their cleansing fluid. In its manifold relations 
to the tissues, in its function of giving and receiving on so many 
sides, there arises constant change in the quantity and composition 
of the blood, limited, of course, within certain bounds and relations 
set by the tissue requirements. When blood is lost, fluid is taken 
into the vessels from the tissues and corpuscles are supplied by the 
blood forming organs to the eventual restoration of the blood. 
When an excessive amount of water is absorbed there follows rapid 
excretion of the superfluous quantity through the kidneys ; and in 
analogous fashion the variations in its chemical constitution are 
continually undergoing adjustment. We have yet to discover 
wherein lies the exact and delicate regulation of the quantity and 
quality of this complex liquid ; at all events the changes in 
chemical composition involve continually repeated stimulation of 
the nerves of the blood vessel walls, of the cells of the hemopoietic 
organs and all secretory cells upon which the hsemic composition 
depends. As soon as this regulation is disturbed the variations 
in the volume and proportionate composition of the blood deviate 
from the physiological limits, and hsemic anomalies* are said to 
exist. 



♦The word clyscrasia was formerly employed in this connection, but was without 
exact significance, being applied by some to any blood abnormality, by others to long 
persisting faults in the proportionate presence of its constituents or simply to 
impurities of the blood from the presence of special substances. The word may be 
dispensed with. 



Plethora and Oligemia. 157 

It can readily be appreciated why there are so many types and 
degrees of blood abnormalities when it is recalled that of neces- 
sity pathological changes in the blood must follow any alteration 
in the efficiency of the organs, the metabolic processes of which are 
constantly removing from or adding to the blood so many elements. 

The amount of blood obtainable from the domestic animals at 
slaughter is subject to such wide variation, as Bollinger and Berg- 
man have pointed out, that it is clear that we can have no safe 
basis for determining the existence of an excessive volume, of a 
condition which may be termed full bloodedness or plethora, in any 
subject, either from the quantity obtained at slaughter or deduced 
from symptoms. The healthy animal very quickly gets rid of ex- 
cesses introduced experimentally into the body, whether it be 
blood of the identical species, blood serum or indifferent fluids ; and 
the transient plethora caused by transfusion causes no disturbances 
worth mentioning. The blood vessels are in fact never filled to 
their full capacity collectively ; the vast multitude of capillaries 
capable of further dilatation can accommodate a large volume of 
fluid in excess of their ordinary content. Experiment upon ani- 
mals shows that in dogs the blood volume may be doubled by 
transfusion, a quantity representing, eight to twelve per cent, of the 
body weight introduced, without injury to the animals ; danger to 
life occurs only after the introduction of a still greater amount 
(Samuel). The excess of fluid transudes from the vessels and is 
eliminated from the body in the course of a few days with the 
urine; the superfluous blood cells are destroyed in the liver and 
other organs. Whether a plethora of actual pathological signifi- 
cance ever occurs in animals is quite unknown. 

Diminution of the volume of the blood, known as blood 
impoverishment, oligaemia or general anaemia, has associated 
with it a decrease of the number of blood corpuscles, known 
technically as oligocythemia; usually, too, the converse is true. 
From a practical standpoint it is difficult to draw any fine distinc- 
tions as to whether the blood is normal as far as the volume of its 
fluid is concerned and only the cellular elements deficient, or 
whether the plasma, its salts and other constituents have under- 
gone the greater reduction ; for which we are accustomed to regard 
the loss and destruction of the erythrocytes, the most conspicuous 
of the blood constituents, as the principal pathological feature. In- 
asmuch, however, as there is a close interrelation of these altera- 
tions, the one dependent upon the other, there are apt to exist many 



158 Disturbances of the Blood. 

peculiar phenomena in these instances, which have thus far been 
imperfectly studied ; for example, the red blood corpuscles may 
undergo reduction and disintegration because the plasma contains 
some unusual saline or an excess of water or because some spe- 
cific haemolytic substance has become mingled with it. Briefly 
speaking, it is customary to speak of general anaemia in a subject 
whose mucous membranes and skin persistently appear very pale, 
whose muscular tissue and viscera have at autopsy the pallor char- 
acteristic of a slaughtered animal and in which in life there ex- 
isted a condition of general weakness. The contrast between 
the peculiar tint of the organs and the deep red color given by the 
full capillary blood serves better to indicate the reduction in the 
volume of the blood than the amount which can be obtained in 
the heart and large vessels and which can be estimated only with 
extreme difficulty. Oligocythemia is determined for a cubic milli- 
meter of blood by microscopic counts of the cells with special 
measuring apparatus ; diminution of the haemoglobin content can 
be determined only by chemical methods. [Clinically this latter 
is estimated by comparison of either the whole or the diluted blood 
with standard color scales, each graduation of tint representing 
a certain proportion of haemoglobin. Matching of colors always 
involves a large personal equation and at best can only be approxi- 
mate, even were it established that the supposedly standard refer- 
ence scale were entirely correct — which is not the case. How- 
ever, as an approximation only and as a fairly ready means of 
comparison, these color tests have at least a clinical value.] 
The least complicated form of oligaemia is that occasioned by 
blood loss from injury to the vascular apparatus, hcemorrhagic 
ancemia, following wounds and lacerations of the vessels, venesec- 
tion or the removal of blood by blood sucking parasites. A blood 
loss exceeding three per cent, may be dangerous to life (external 
or internal injuries) and sudden haemorrhages of still smaller vol- 
ume from the large vessels may be fatal. [While exceptionally 
this statement may be true where there are other factors as nerv- 
ous shock involved, the limits of non-fatal blood loss as here given 
are for ordinary cases quite too low. As much as one-third the 
volume of blood has often been withdrawn without fatal collapse.] 
The volume of fluid lost by non-fatal haemorrhage is soon 
restored by absorption of water from the tissues and ingesta; while 
the corpuscles and albuminous material are reformed in the course 
of a few weeks or months. In fatal haemorrhage there occur 



Changes in the Erythrocytes in Ancemias. 159 

phenomena of suffocation, lowering of blood pressure and uncon- 
sciousness (anaemia of the brain). After haemorrhage proteid 
metabolism is increased ; metabolism of fats is, however, decreased 
because of the diminished power of combustion. Hence repeated 
venesections are appropriate treatment where it is desired to in- 
crease the deposition of fat and they are employed as aids to fat- 
tening animals. 

General anaemia may also be brought about by insufficient nutri- 
tion or improper assimilation of food, as well as by diseases and 
injuries of those tissues which supply definite blood constituents. 
Here are particularly included various affections of the stomach and 
intestine, hepatic diseases and alterations of the lymphatic tissues ; 
but in addition to such disturbances there is a wide further possi- 
bility of the establishment of an anaemia from disease of the many 
other tissues which contribute to blood formation. A number of 
agencies are known to be capable of inducing the condition by caus- 
ing the destruction of the blood corpuscles, perhaps to such a de- 
gree that regenerative effort can no longer efficiently restore the 
loss, as certain parasites of the blood (trypanosomes) and poison- 
ous or toxic products of metabolism. 

Among the most notable symptoms of many anaemias are 
changes in the form and structure of the erythrocytes. In place 
of the circular discs there may be met irregular pyriform, club- 
shaped or indented elements of various size, cells containing 
vacuoles (cavities, hollow spaces), and nucleated red corpuscles. 
A blood preparation showing such multiform cells of varying ap- 
pearances is said to exhibit poikilocytosis (toikCKos, variable, con- 
fused, involved). Recently alterations in the staining reactions 
of the corpuscles have been made out. The normal cells invariably 
take up only one tint from certain staining combinations ; the 
stroma of young forms, degenerating and dead cells, however, 
may assume several colors (polychromatophilia). The occurence 
of nucleated red corpuscles in the circulating blood is an evidence 
of active regeneration of these elements, and is often encountered 
in the anaemias. Especially large cells of this type are sometimes 
met (megaloblasts, gigantoblasts) , a peculiarity interpreted as 
evidence that regeneration is taking place with extreme haste, 
such cells, otherwise only seen in -the bone marrow as early stages 
of the erythrocytes, entering the circulation in these cases as im- 
mature elements (Krchl). The increased cellular multiplication 
in the bone marrow, the principal site of the formation of enthro- 



160 Disturbances of the Blood. 

cytes, causes in anaemias large areas of this tissue to return to the 
condition of red marrow (normally only young growing animals 
have much red marrow ; in adults medullary blood formation is 
limited to a few bones according to the amount of blood required 
to be formed; change of the marrow to the red state and pro- 
duction of this condition in many of the bones may be brought 
about in animals by venesection — Naunyn, Litten and Orth). 

In severe forms of anaemia not occasioned by actual blood loss the pro- 
portion of iron in the liver, spleen and kidneys becomes abnormally high, this 
feature invariably indicating exaggerated destruction of the red cells. 

From a variety of causes, particularly the influence of certain 
poisons (salts of the biliary acids, snake venom, bacterial toxines) 
and, too, the transfusion of heterogeneous blood (blood from a 
different species of animal), the haemoglobin may undergo solution 
and separation from the erythrocytes into the plasma (hcemo- 
globincemia) . The coloring matter thus freed gives the plasma 
or serum a diffuse wine-red color. A portion of the haemoglobin 
is taken up by the liver and transformed into biliary pigment, and 
the remnants of the injured and therefore disintegrating blood 
corpuscles are to be found in the liver and in the spleen (also in 
the marrow), these organs sometimes becoming considerably swol- 
len and excessive bile formation taking place. The bulk of the 
liberated haemoglobin is removed by the kidneys, causing more or 
less harm to these organs and giving to the urine a blood red to 
black discoloration (hcemoglobincemia). These changes are ob- 
served not only in association with severe infections and intoxica- 
tions in cattle, but are also seen after muscular strain and chilling, 
especially in horses and, too, in human beings (infectious, toxic, 
paroxysmal, myogenous, rheumatic haemoglobinuria). Some of 
the haemoglobin in haemoglobinaemia which remains in the blood is 
converted into methaemoglobin ; this change may also affect the 
coloring matter within the corpuscles, and is apt to result par- 
ticularly from the action of certain poisons (antipyrin, potassium 
chlorate). It gives rise to an appreciable sepia-brown coloration 
of the blood (methcemoglobincemia) . There always coexist with 
this group of blood changes serious diseases of the subject; the 
haemoglobin, freed from the cells and altered in its constitution, 
useless for respiratory purposes, is no longer capable of taking up 
and giving off oxygen (Krehl), and the disintegrating blood cells 
give origin to substances which may cause coagulation to take 



The Leucocytes in Ancemias. 161 

place here and there in the vessels, occlusion of the capillaries 
and serious lesions of the renal epithelial cells. 

Oligemia is occasionally associated with a truly watery condition of 
the blood, as where in case of haemorrhage, blood impoverishment, inani- 
tion, or renal disease the blood becomes deficient in albumen, the vessels 
become filled with the fluid from the tissues in an effort to restore the 
deficiency; such a condition is termed hydremia (oligemia serosa). So. 
too, the increase in the proportion of water with increase of the total 
volume of blood (plethora aquosa, serosa) may be thought of as a 
pathological possibility; however, proper information is as yet lacking 
concerning these pathological conditions and the relation between quanti- 
tative changes of the serum albumen to the proportion of water in the 
blood. Normally, large excesses of water known to be rapidly absorbed 
from the stomach and intestine into the blood are quickly passed off 
through the kidneys. 

Of the pathological conditions of the leucocytes or white blood 
cells and their reduction or increase in numbers in the circulating 
blood our knowledge is only of the most superficial character. 
To what extent the morphological and tinctorial peculiarities of the 
individual forms and groups of leucocytes and lymphocytes nor- 
mally found in the blood are characteristic of the origin and of the 
role of these cells is a matter requiring further investigation. 
These cells are of especial interest to the pathologist from the fact 
that they are either attracted or repelled by chemical materials in 
the tissues and by various particulate elements which may give 
origin to the former (positive and negative chcmotaxis). Be- 
cause of the power possessed by these cells of approaching or 
receding from a given point like motile organisms, of taking Into 
their substance small bodies which they encounter — an act which 
is to be regarded as an attempt to obtain nourishment (cellular 
devouring capacity, phagocytosis) — they may be thought of as 
playing the part of "scavengers of the organism" (products of 
disintegration, dust particles, dead cells and tissues, dead bacteria, 
etc., all being removed in this manner). They may however by 
identically the same mode of action come to serve as carriers of 
infection in case a living bacterium or animal microorganism hap- 
pen to be taken up by them. A microorganism not necessarily 
destroyed in the substance of the leucocyte, but possibly actually 
multiplying there, may be carried away to a now situation and 
there renew its toxic influences, especially if the phagocytic cell he 
destroyed by its poison. [Metschnikoff urges strongly (hat after 
appropriation of a microbe by a phagocyte, the former may be 



162 Disturbances of the Blood. 

regarded as entirely destroyed or as seriously impaired in its' 
vitality.] It is readily observed in suppurations undergoing 
metastasis (cf. metastasis), in swine erysipelas and other bac- 
teriaemias, that many of the leucocytes are loaded with the specific 
germs. 

Negative chemotaxis, too, the movement of the leucocytes away 
from certain poisons or more frequently the mere failure of attrac- 
tion of the cell toward these substances, is capable of explaining a 
number of points connected with disease and immunity. For ex- 
ample, as shown by the extremely interesting studies of Besson, 
Leclainche-Vallee, Vaillard and Vincent, non-virulent but living 
germs (spores) of tetanus, malignant oedema and blackleg are 
englobed by leucocytes and ingested and thus prevented from de- 
velopment and from becoming virulent; virulent germs of these 
same sorts, however, prevent the leucocytes from entering the tis- 
sues because of the toxines to which they give origin and are 
therefore not taken up by the phagocytes, but continue their harm- 
ful action upon the tissues in which they exist. 

The general group of leucocytes in the blood is subject to con- 
siderable variation in number, even under normal conditions. 
After taking food or violent muscular exercise there may be 
uniformly observed an increase in their number (physiological 
leucocytosis or hyperleucocytosis), apparently occasioned by the 
attractive influence exerted by various proteid matters, fatigue 
stuffs, etc., which have entered the blood. In inflammations, sup- 
purations, and infectious fevers a similar increase in the number 
of leucocytes distributed throughout the blood occurs (pathological 
hyperleucocytosis) , similarly ascribable, so far as indicated by ex- 
periment, to chemical attraction and the circulation in the blood 
of substances stimulating the leucocyte-forming tissues to greater 
production. (Injection of bacterial proteins and other proteids into 
the blood is particularly likely to be followed by hyperleucocytosis). 
[While there are a few exceptions to the usual occurrence of 
leucocytosis in acute infections, it is in a general way to be in- 
terpreted as an unfavorable feature when such increase fails to 
take place (leucopenia) ; either the subject being in such deterio- 
rated state that the usual reaction is impossible and the resistance 
to the disease much below par, or the smallness of number of these 
protective cells itself determining the failure of sufficient antago- 
nism. Cases marked by such unusual leucopenia, with the excep- 
tion as above suggested of a few special forms of disease, are apt 
to terminate fatally. 



The Leucocytes in Ancemias. 163 

To a certain extent the increase of this or that particular form 
of leucocyte is of diagnostic importance. In brief we recognize 
as the most common form of white blood corpuscle the polymor- 
phonuclear neutrophile cells (containing multiple nuclei or a single 
polymorphous nucleus, and having numerous fine granules in the 
cytoplasm which elect a combination of the acid and alkaline dyes 
in staining with such mixtures, becoming purplish with methylene 
blue and eosin for example). An increase of these elements, 
spoken of simply as leucocytosis or hyperleucocytosis according to 
its grade, is commonly met in a number of infections, particularly 
those of the septic group. There are normally present in the 
blood a few similar leucocytes which have, however, in their 
cytoplasm rather coarse granules which, from an acid and basic 
combination of dyes, select the former, being therefore called 
oxyphile cells (or because eosin is the acid part of the common 
methylene blue and eosin solutions and their cell granules appro- 
priate the red of the eosin, these cells are often called eosinophile 
cells). These oxyphile cells may become increased in a number 
of conditions, but this increase, known as eosinophilia, is especially 
notable in the blood of animals or human beings subject to some 
of the animal parasites as the trichina or hookworm. In pseu- 
doleukemia and lymphatic leukaemia the lymphocytes, cells with 
single large, deeply basic staining nuclei and with fine basophilic 
granules in the scanty cytoplasm, are especially increased. In the 
common lieno-medullary leukaemia there is special increase in a 
large type of leucocyte not normally present in the blood but 
natural to the bone-marrow, known as a myelocyte, with large 
nucleus taking the basic stain faintly and with fine neutrophilic 
granules in the cytoplasm.] 

Where there is such an increase of leucocytes in the blood that 
they equal or exceed the number of erythrocytes in the drop from 
which the cell count is made, or if certain cells normally present 
in but meager numbers are unusually numerous [the mononuclear 
cells above noted as myelocytes] the name leukcemia is employed 
to denote the condition. [The actual number has been known 
to equal that of the erythrocytes, but this is exceptional ; and the 
present conception of leukaemia concerns rather the type of cell 
present in the blood, the myelocyte, than the actual numbers at- 
tained.] In this disease the blood is apt to be changed in its 
macroscopic appearance as well, becoming of a light red or rasp- 
berry color. There also occur hyperplastic changes in the various 



164 Disturbances of the Blood. 

lymphoid structures of the body (lymph glands [in lymphatic 
leukaemia] ; bone-marrow and spleen [in lieno-medullary leu- 
kaemia] ) ; and the coincidence of a general debility, fever, and 
tendency to haemorrhage mark the condition as a serious affection. 
Nothing definite is known of the aetiology of the affection either 
in man or the animals ; it has been conjectured, however, that the 
cause may be of an infectious nature. 



DISTURBANCES OF M'ETABOLISM; RETRO- 
GRESSIVE AND NECROTIC PROCESSES 

Faults of Heat Regulation; Hyperthermia; Fever. 

The temperature peculiar to the various warm-blooded animals 
is constantly maintained in health at the same level within narrow 
limitation by the delicate and accurate regulatory mechanism of 
the body. With every change in the surrounding temperature and 
other external influences there occurs special adaptation of heat 
production and heat dissipation on the part of the animal body. If 
an excess of heat be produced within the body from exaggeration 
of metabolism (muscular activity, ingestion of large amounts of 
food), excessive heat dissipation follows; the cutaneous blood ves- 
sels dilate and the system loses in consequence a greater amount 
of heat from its surface by conduction, by radiation and if need be 
by perspiration, as well as by free evaporation of moisture in the 
lungs. In case the body suffers unusual heat loss (cold environ- 
ment) heat dissipation is diminished by constriction of the cutaneous 
vessels, and the chemical activities in the tissues increase heat pro- 
duction by accelerating decomposition, that is, the combustion of 
carbohydrates and fats, particularly in the musculature. Rich 
food supply and bodily activity increase the production of heat ; 
and by these means and by simple diminution of heat dissipation 
the warm blooded animal is enabled to maintain its proper tem- 
perature in spite of marked chilling. 

The human being in state of health, possessing additional means 
of conserving his warmth by a number of layers of warmed air 
(clothes) about his body, maintains an average body temperature 
of 37.2 — 37. 4° C, the variation from morning to evening being 
about one or one and one-half degrees. The horse, according to 
Friedberger-Frohner, has a normal temperature of 37. 5 — -38.5° C. ; 
the cow, 38 — 39 C. ; the sheep and goat, 39 — 40.5 C. ; hog, 



i66 Temperature Disturbances, 

38°— 40° C; dog, 37-5°— 39° C; cat, 38 — 39 C. ; birds, 

41.5 — 42-5° c. 

The warm blooded animal maintains the constant physiological 
level of temperature by the continued operation of the heat dis- 
sipating powers; if there were no such loss, the amount of heat 
production would be sufficient to cause an increment of about one 
degree centigrade in the temperature of the blood every half hour. 

Passive Hyperthermia. By limitation of heat dissipation 
the body may become overheated, particularly when the cause 
is some external physical influence which hinders heat loss by 
evaporation. Although in a dry atmosphere where there is no 
restriction to evaporation the body is capable of enduring even high 
temperatures, of the surrounding air, the body heat increases rap- 
idly in a hot, moist atmosphere, heat loss by evaporation being 
impossible, and all the more if in addition there be increased pro- 
duction from muscular exercise. In a warm bath of 40 — 41 ° C, 
the human body temperature may even in half an hour reach 40 C. ; 
in water of 37 C, it rises about i° C. in an hour, and in an hour 
and a half about 2 C. 

Animals closely packed in hot railway cars experience consid- 
erable increase of temperature ; in warm, damp air animals closely 
herded in long drives (droves of hogs, oxen yoked to wagons) may 
have their temperature reach more than 40°C. Under such cir- 
cumstances where only external physical conditions render the 
regulation of the body temperature impossible or where (perhaps 
coincidently) unusual accession of heat production occurs because 
of exceptional muscular exercise, there is really no true febrile tem- 
perature present, but rather only a passive heat accumulation, 
passive hyperthermia; the mechanism of heat dissipation is acting 
in its fullest capacity and is insufficient only because the demands 
upon it are excessive (Krehl). Thermolysis so far as the animal 
body is concerned is not at fault ; but fails because of conditions 
existing in the external surroundings. 

Whether pathological results follow such passive hyperthermia 
will depend upon the persistence of the condition and the subject's 
power of adaptation. Men and animals living in tropical coun- 
tries give evidence upon this last point ; and, too, it is commonly 
seen that when a number of individuals are subjected to excessive 
temperatures there are only certain ones who suffer pathologically, 
those probably whose thermo-regulatory mechanism is of inferior 
efficiency. Passive hyperthermia may reach 42 ° — 45 ° C. and may 



Fever. 167 

terminate fatally {heat stroke). The occurrence of a heat stroke 
is marked by symptoms of general weakness, dizziness, fainting 
attacks, and marked acceleration of the pulse, these probably being 
mainly dependent upon disturbances of brain and myocardium, al- 
though upon this point there is need of further study. 

Fever (febris, from fervere, to be hot) is a state of the body 
in which because of some disturbance of metabolism the regulation 
of the body temperature to a mean level has ceased. The chief 
and most constant evidence of fever is the abnormal increase of 
the temperature of the blood, or internal body temperature. This 
febrile hyperthermia or fever heat may exceed the normal tem- 
perature of the animal perhaps but half a degree or by from 
two to five degrees centigrade. It is characterized by marked re- 
sistance to influences causing heat dissipation and by considerable 
variation ; and is accompanied by increased tissue waste, changes 
in the type of and increased frequency of the arterial pulse, increase 
in the rate of respiration, diminution and alterations in the various 
secretions, particularly in the urine, disturbances in the sensory 
apparatus, increased thirst and loss of appetite. This group of 
symptoms, which occur with the heightened temperature and with 
it go to make up the clinical picture of fever, are to a slight 
extent directly dependent upon the increased temperature of the 
blood (for example, the number of cardiac movements and respira- 
tions), but for the greater part are the results of the complex 
action of the causes of the fever. The main point in the conception 
of fever, with its febrile excess of temperature, is that the latter 
is not the mere result of external physical influences restricting 
thermolysis, or of muscular activity, but that there are certain 
metabolic processes in operation which are due to the presence of 
special temperature producing substances (pyrogenetic substances) 
which give origin to the hyperthermia. How the heat equilib- 
rium is affected by such substances, whether they directly dis- 
engage the heat from the cells and cellular groups or whether 
they act indirectly through a heat centre, is not as yet certain and 
cannot even in a general way be explained. These pyrogenetic 
substances vary much among themselves and the reactions which 
they give rise to are by no means uniform. Fever may be thought 
of as an indicator (Wassermann) that some peculiar metabolic 
processes are in operation in the body accompanied by tissue 
destruction and the production of antitoxic and bactericidal sub- 
stances and precipitins ; and may be considered as an associated 



168 Temperature Disturbances. 

or partial manifestation of a complex reaction to which the or- 
ganism is prompted by the invasion of substances foreign to the 
system. From this it may be appreciated that the idea of febrile 
temperature and of fever is in reality principally based on the 
aetiology of the condition ; the existence of proper causes of fever, 
the presence of pyrogenetic substances, is the factor determining 
whether we are or are not to regard and speak of a hyperthermia 
as febrile. 

Microorganisms, both vegetable and animal, constitute a most 
important group of these pyrogenic substances, acting especially 
through their chemical toxic products. It is this fact which ex- 
plains why the course of nearly all the acute infections is accom- 
panied by fever. It can be promptly induced by infection with 
various specific germs ; inoculation with anthrax bacilli or pyogenic 
cocci, with trypanosomes or piroplasmata, each occasions a febrile 
reaction. After Charrin and Ruffer pointed out that, by injecting 
into rabbits cultures of bacillus pyocyaneus which had been 
sterilized and freed from living germs, febrile temperature acces- 
sion may be induced, a number of observers have demonstrated 
that similar effects may be obtained by employing the metabolic 
products of a number of other bacteria. This means therefore 
that we are here dealing with a group of soluble substances passing 
from the substance of the microorganisms into the fluids and tissues 
of the affected body, either secreted by the living bacteria or 
representing some of the results of disintegration of the bacterial 
body (toxines, proteins, alkaloids and a variety of substances of 
different composition). According to E. Centanni, practically the 
entire group of bacteria produce a practically uniform fever toxine 
which he isolated from cultures and named pyrotoxina bacteritica. 
and with which he was able to reproduce in rabbits all the main 
clinical features of the infectious fevers. 

This thermotoxine is, however, produced in varying quantity 
by the individual types of bacteria ; injection of definite doses of 
some forms of bacteria and culture filtrates occasioning no febrile 
reaction ; some only after large doses ; others causing high fever 
with the employment of extremely small amounts. Another 
feature to be considered is that various kinds of bacteria known 
to elaborate thermogenic substances do not act with uniformity 
in the production of fever in all kinds of animals, and different 
animals show even less uniformity in their susceptibility to the 
fever toxines (Krehl) ; from which it may be assumed that the 



Fever. 169 

pyrogenetic substances of the different bacteria also have a 
qualitative variation, are just as different and specific as for 
example diphtheria toxine and tetanus toxine (Wassermann). The 
pyrogenetic power of bacteria is not in any way related to their 
pathogenicity (Kraus) : there are bacteria of high grade viru- 
lence which produce but little febrile disturbance (as tetanus 
bacillus), and on the contrary there are non-pathogenic microbes 
whose cultures nevertheless exhibit a (transitory) pyrotoxic 
activity, as those of bacillus prodigiosus and bacillus subtilis 
(Voges). A number of bacterial products when administered to 
the smaller experiment animals in but small doses give rise to 
increase of body temperature, while in large doses they cause it to 
fall below normal ; and there is a notable peculiarity in the action 
of the substances obtained from cultures of the tubercle bacillus 
and the glanders bacillus, very small doses of extracts of these cul- 
tures causing fever to occur in tuberculous and glanders animals 
but not in healthy ones (in the -latter, however, a rise in tempera- 
ture is produced when the extracts are given in large doses, which 
would on the contrary produce depression of temperature in the 
diseased animals with symptoms of fatal intoxication). 

According to the experiments of Matthes the sterile, salt-free 
hydration products of the albumen molecule, protalbumose, 
deuteroalbumose, peptone, act in the same manner as the last named 
agents, and it seems that in the protoplasm of all living cells 
there exist certain proteid substances capable of inducing temper- 
ature accession when injected or when set free in the body (Kraus, 
Wassermann). By subcutaneous and intravenous injection of 
blood or blood serum of a different species of animal, or by intro- 
duction of iodide of potash solution or pure distilled water it is 
possible to cause a rise of temperature, a phenomenon depending 
upon the hemolytic influence of these substances, either the 
haemoglobin thus freed or the fibrin ferment formed occasioning 
the increase of temperature. The injection of fibrin ferment 
promptly occasions marked increase of temperature, true also of 
other ferments (pepsin, rennet, pancreatin, invertin) as well as 
of the animal secretions (milk, urine). The purified enzymes are 
apparently inert; but the same ferments in impure state (but 
sterile), presumably containing some albuminous admixture, induce 
an elevation of temperature from which it may be inferred that 
the active principles are some type of albuminous body (Krehl). 
However, the influence is not the property of au\ one single albu- 



170 Temperature Disturbances. 

minous substance, various proteins, bacteria and other microorgan- 
isms, the products of disintegration of red and white blood cor- 
puscles and other tissue elements all possessing the same influence. 

Foreign albuminates always give rise to the development of 
protective processes, of phagocytosis and the production of specific 
antibodies. Certain organs like bone marrow, spleen and lymph 
glands are stimulated to special activity by the presence of these 
foreign substances manifesting cellular hyperplasia (mitotic nuclear 
figures) and probably producing special secretions. This increase 
of their physiological activity is necessarily associated with 
increased metabolism and the latter must occasion elevation of 
temperature. The relation between the production of antibodies 
and febrile attacks is very striking in many of the infectious dis- 
eases. For example in case of pneumonia in human beings it is 
known that in the course of the fever protective bodies are formed 
in the bone marrow and that the fever diminishes as these sub- 
stances begin to manifest their bactericidal action. After the crisis 
these protective substances are found in considerable amounts in 
the blood (Klemperer, Wassermann). In recurrent fever of man 
the onset of the fever takes place as soon as the organisms appear 
in the blood ; protective bodies are then formed by reaction of the 
body cells and with their accession to the blood the microorgan- 
isms are destroyed and the fever falls ; if these are removed the 
spirilla return from their foci of deposit to the blood and the fever 
returns. In other examples the beginning, rise and fall of the 
fever are apparently dependent upon definite stages of develop- 
ment of the infectious agents ; in human malaria the fever begins 
as soon as the parasites reach the phase of sporulation and is 
checked if by the administration of quinine the maturation or rup- 
ture of the sporulating organism is prevented. 

The connection of fever production with substances foreign to 
the body (infectious and toxic) is so clear that if an animal mani- 
fest febrile symptoms it seems a permissible conclusion that there 
must be infectious or toxic substances circulating in its blood. 
Often the fever is the only manifestation of the disease appreciable 
during life to indicate the existence of an infection (essential 
infectious fever) ; usually it appears as a precursor of other symp- 
toms of the infectious cause (prodromal fever), or accompanies 
local or general disease processes (secondary fever, traumatic 
fever, pycemic, septicemic, hectic fever, inflammatory fever) ; and 
may also develop after the employment of therapeutic measures 



Fever. 171 

which introduce pyrogenetic substances into the body or occasion 
their production in the system {infusion fever, deprivation fever). 

The question has been asked whether fever is useful or harm- 
ful to the body and whether it may not possibly have the definite 
purpose of rendering infectious and toxic matters harmless. From 
the fact shown by various experiments that temperatures from 40 to 
42 ° C. may inhibit the growth of a number of bacteria, attenuate 
their virulence or actually destroy them it has been conjectured 
that the same effect is produced in the body by febrile hyperther- 
mia, that the fever, "purifying by fire" as it were, is in reality a 
factor in causing recovery. There are a number of experiments 
which seem to uphold this idea ; small experiment animals have 
been shown to bear better (that is do not die as soon from) diph- 
theria, chicken cholera and other infections if kept in an incubator 
at 41 to 42 C. than when left in a lower atmosphere. The resistance, 
however, does not depend upon the direct action of the higher tem- 
perature on the microorganisms, as Wassermann has pointed out, 
but upon the fact that the body when kept warm is better able to 
permit the action of its natural protective mechanism (phagocyt- 
osis, antitoxine production). There is no evidence of anv pur- 
pose for the increased temperature ; this is only a symptom and 
a result of the exaggerated metabolism, and the favorable outcome 
is brought about by the reactive production of antibodies. In a 
similar manner the complications and sequels of a fever are not 
to be imputed to the elevated temperature. Of course, it does 
cause increased rapidity of cardiac action and of respiration, loss 
of appetite and perhaps parenchymatous changes ; but the real point 
of the fever is in the severity of the infection, in the toxic action of 
the infectious microorganisms which contribute the real danger, and 
the elevation of temperature is only the index of the latter. The 
result of measures having for their purpose the reduction of tem- 
perature (cold water treatment and antipyretics) is not in conflict 
with this conception of the relative inutility of the tem- 
perature in fever; such measures manifest their beneficial influence 
not only by reducing the temperature but also by inhibiting the 
causes and by diminishing metabolism. 

Stages of Fever. The febrile course is usually separable into a 
number of periods or stages. The inception of the fever, its initial 
period {pyrogenetic stage, stadium iiicrcmcnti, chill stage) mani- 
fests itself by general symptoms of fatigue, weakness, roughening 
of the hairy coat, loss of appetite and rise of the internal tempera- 



172 Temperature Disturbances. 

ture. In a number of affections it is marked bv chills (trembling 
and shivering throughout the body) ; during the paroxysm, the 
internal temperature_is elevated from the first and continues high, 
while the skin of the peripheral parts shows a lack of uniformity 
in temperature, the feet, for example, being cold, the muzzle in 
cattle and the nose in dogs, hot. The action of the heart is acceler- 
ated, the pulse correspondingly increased in frequency, small and 
tense ; and the respirations increased in number. The cause of the 
chill is to be found in the spasmodic constriction of the cutaneous 
vessels occasioned by the poisonous products of the infectious 
agents ; the loss of appetite and the occasional vomiting (in dogs) 
may also be ascribed to a toxic influence acting upon the nervous 
centres (Blumenthal). The initial or chill stage lasts for from 
half an hour to two hours, or, in cases where chills are absent, 
for several days. The heated stage which follows, varying in dura- 
tion with the particular disease from a few hours to a number of 
weeks, is that in which the temperature elevation reaches its maxi- 
mum level ; it is known as the fastigium or acme (stadium acmeos). 
In the remittant type, characterized by alternations of depressions of 
the febrile temperature (remissions) and succeeding reaccessions 
(exacerbations) , the elevation of temperature manifests a number 
of maximal points. The other symptoms keep pace with the hyper- 
thermia (loss of appetite, increased thirst, general weakness, 
diminution of the secretions, acceleration of respiration and pulse 
rate, hot, dry skin). The intensity and duration of the fastigium 
are expressive of the severity of the febrile disease, and estimated 
by the height of the temperature and the strength of the heart's 
action. In a moderate fever the temperature should not rise beyond 
40° C. ; an intense fever is characterized by an elevation exceeding 
40- C. A fever in which the cardiac action is strong and the pulse 
tension high is said to be sthenic ; where the cardiac beat is weak 
and without force and the pulse soft the fever is spoken of as 
astlienic. 

In the period of febrile decline (stadium decrements or deferves- 
cence) the body temperature returns to normal and the associated 
symptoms .diminish in their intensity. In case the fall of temper- 
ature takes place rapidly (in a few hours or at the most within 
three days), sometimes with marked perspiration and profuse 
excretion of urine, it is spoken of as crisis. Sometimes just before 
defervescence there are noted special exacerbations of the febrile 
state (perturbatio critica) ; incase there is a period of several days' 



Fever. 173 

duration in which there is alternation of notable depression and 
exacerbations of temperature it is spoken of as an amphibolic stage. 
The slow and gradual type of defervescence is called lysis or reso- 
lution. The decline of fever is believed to be due to the formation 
somewhere in the organism (bone marrow, spleen, liver, etc.) 
during the febrile process of a large quantity of protective sub- 
stances and to the destruction of the pyrogenetic substances present 
in the system from the time when these protectives become predomi- 
nant. Should the blood become rapidly filled with protective sub- 
stances from the sites of antitoxine production or with phagocytic 
elements from hyperleucocytosis, the change in the case comes on 
suddenly, (crisis) in the first, or gradually (lysis) in the second 
instance. The termination of the fever, at which time the normal 
temperature again prevails or merely trifling variations continue, 
brings back the appetite ; the pulse recovers its softness and even- 
ness ; the functions of all the organs proceed as before the attack ; 
and there persist for a time only weakness and general debility. 
This is known as the period of convalescence. In case, however, 
the febrile disease go on to an unfavorable termination, and there 
appear irregular fluctuations in the temperature curve, a sudden 
rise far above normal or a subnormal depression, with signs of 
impending death, we are then dealing with what is known as the 
premortal [moribund] stage [cf. p. 95]. 

When the stages above mentioned succeed each other in the 
order indicated the course of the fever is said to be regular or 
typical; if there be variations, it is said to be irregular or atypical. 

If in this regular course, a fever should continue for only a few 
hours or for a day, the whole process ending within this time, it is 
described as an ephemeral fever. A fever of one or more weeks' 
duration with a temperature curve showing daily an evening rise 
and a morning fall comparable' to those of the normal body tem- 
perature, but at a level above that of the normal internal tempera- 
ture, is said to be a continued fever; where the depressions and 
exacerbations are more pronounced it is called discontinuous or 
remittent. When the variations in temperature are so great that 
between the times of high temperature accession, which take place 
periodically (febrile paroxysms) , there occur periods of absence of 
fever (apyrcxia) , the fever is said to be of an intermittent or 
recurrent type. 

Metabolism in Fever. The causes of fever are known to give 
rise as a rule to increased destruction of the albuminates, essen- 



174 Temperature Disturbances. 

daily an increase of oxidation (increased consumption of oxygen). 
As a result of this heat production is increased. 

There is, however, a well defined type of fever in which there is 
no recognizable increase of heat production (Krehl), the febrile condition 
resulting solely from diminution of heat dissipation. 

This increase exists at the time of the initial stage and is marked 
during the chill, the muscular contractions in this phenomenon add- 
ing to the heat production. Heat dissipation is also increased in 
fever; otherwise the temperature would continue to progressively 
rise throughout the attack (Krehl). Dissipation is, however, less 
than production. (It is only in the period of invasion that heat 
dissipation is with any uniformity diminished, in the chill, by the 
constriction of the cutaneous vessels.) 

The increased albumen destruction by oxidation is shown by 
the increased nitrogenous output in the urine, the increased elimina- 
tion of carbonic acid and the lessened oxygen elimination. Coinci- 
dently there is a retention of water ; Senator has shown that of the 
ingested fluids, only one-third or less appears in the urine, a cir- 
cumstance which cannot be explained by the amount lost by evapor- 
ation from the skin (v. Ley den). The water may be supposed to 
be used to keep in solution the large accumulation of products of 
the increased metabolism in the tissues ; this idea receives corrobora- 
tion in the fact that after the crisis when the retained substances are 
being eliminated there occurs a polyuria without increase of inges- 
tion of water (Blumenthal). A large part of the nitrogen produced 
by the increased albumen destruction must come from the blood, the 
disintegration of the latter being the cause of the high proportion 
of potassium and urobilin met in the urine (Blumenthal). The uric 
acid excretion is also increased, from which may be inferred a 
marked destruction of the nucleo-albumens (Blumenthal). 

Probably not all of the products of tissue disintegration are 
eliminated from the system or consumed ; the urine does not con- 
tain everything which underwent disintegration in the organism. 
Probably during the fever some of its products are employed for 
tissue reconstruction or in the formation of antitoxines. The 
chlorides, phosphoric acid and sodium are found in the urine in 
smaller proportion than normally. With the critical decline of the 
fever, the tissue destruction ceases and the organism rapidly re- 
stores its nitrogen-containing structures, the nitrogenous excretion 
falling below its intake and a distinct increase in body weight 
ensuing (Blumenthal). Only in cases in which, because of re- 



Fever. 



175 



sorption of exudates (pneumonia), there is a large amout of 
nitrogen to be disposed of, is its elimination in the urine main- 
tained above the usual proportion. As the result of the degenera- 
tive changes which have taken place, fatty acids appear for a time 
in the urine (fatty degeneration) ; and after a time sodium chloride 
may be again found in large amounts. 

In all febrile affections the kidneys are particularly likely to 
be affected. The poisonous bacterial products, and the substances 
of greater or less toxicity which come from tissue destruction are 
irritative to these organs, and render the glomeruli and renal 
epithelial cells permeable to albumen. ' As a rule an albuminuria 
of variable importance is established, an evidence of the existence 
of a nephritis of an exudative type. 





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Fig. 18. 

Continued fever; epidemic pleurisy in a five-year-old horse (after Friedberger — 

Frohner). 

In some cases acetone is found in the urine, considered by some 
authorities as indicative of fat consumption, but regarded by Blumenthal 
as originating from proteid through bacterial influences and oxidation. 
[Acetone, diacetic acid and oxybutyric acid are all occasionally encoun- 
tered in the urine in febrile states, just as in case of diabetes mellitus, 
and there is reason to suppose that in both conditions faults of carbo- 
hydrate metabolism underlie their occurrence, although it is possible that 
such substances may in less direct manner be products of fat or proteid 
destruction, as above suggested.] The origin of diazo bodies (diazo 
reaction of urine) has been attributed (Ehrlich) likewise to bacterial influ- 
ences (in man in tuberculosis, typhoid fever, measles). 

The existence of fever is most efficiently detected by thermo- 
metric measurement of the body temperature. This is performed 
in animals by introducing a suitable thermometer into the rectum, 
or in females into the vagina, allowing it to remain for five minutes, 
after which the degree of temperature may be read off. A single 



176 



Necrosis. 



observation may establish the presence of fever, but observations 
made at regular intervals afford more complete and certain informa- 
tion as to the existence and characteristic features of the fever and 
are necessary in following its course. The normal temperature 
characteristic of the animal must be known, together with the 
subnormal and hypernormal (non-febrile) ranges when in health; 
the differences peculiar to species and age, and the daily physio- 
logical fluctuations. These are dealt with in works on normal 
physiology, to which reference may be made (Cf. Friedberger and 
Frohner, Lehrb. der Minis chen Untersiichtingsmethoden f. Tier- 
drzte). 

The course of the fever can be most satisfactorilv followed bv 



fy 2* * 1 2 3 ¥ 5 6 7 g <? /o // /2 /3 


_h 


II 


11 i 1 


1 \ l\ 


Ui" \ \ jl 1 


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L t 4Xt 1 X 


I \ \ V 


*° e ■*- -il - ilx x x 


r A txxt 


iV- m t j_j t ^i 


LAIX T-izi i4a 


,-. _pi. 1 _!__. 1 A A » ^_ _+_ 


M _T TJn LID x k , 


/ V 1 1 r A 


4 J , [r A 


r / 1 \ A 




srf r x f iz 1 [V , 


\ / \ y) 


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V V \ 


X ' "X iz 


37" 1 



Fig\ 3 9. 

Kemittent fever ; an infectious fever in an eight-year-old mare. 

berger — Frohner. ) 



(After Fried- 



recording the degrees of temperature obtained from time to time 
by thermometric reading upon a chart marked out with abscissa 
lines, each as a point [with corresponding height from the normal 
line according to the number of degrees of temperature observed], 
thereafter connecting these points so as to construct a scale or 
curve of the temperature range upon the chart, the temperature- 
or fever-curve. 

Necrosis. 

Complete death of organs or parts of organs within the living 
body, local death, is known as necrosis (?j vticpuais, death) ; when 
this process of disintegration has associated with it the features 



Causes of Necrosis. 177 

of degeneration it is also indicated by the term necrobiosis. Be- 
tween the degenerations (the retrograde metamorphoses) and the 
necroses it is impossible to draw any sharp line of difference. (There 
are in addition a number of other expressions in use for the special 
types of necrosis by which the death of a part in the living body is 
seen to occur, which are often employed indifferently as synonyms — 
vide infra). Even in normal life in the interchange going on in 
the course of the physiological processes there is a certain amount 
of the cellular material which is being broken down in the tissues, 
consumed and replaced by new cells. The epidermal cells of the 
skin are continually undergoing keratinization, later desquamat- 
ing as dead structures, and newly formed cells from the stratum 
Malpighii take their place to undergo in their turn the same 
change. In the same way the epithelium of various glands die 
and contribute their own substance to their secretions, as the cells 
of the sebaceous and mammary glands. The blood cells are also 
perishable elements, some being all the time in course of disintegra- 
tion and death, the formation of new cells continually proceeding 
in the hemopoietic parts (bone marrow and lymph glands) to 
compensate for this loss. Other physiological instances of local 
death are also seen in the loss of the milk teeth and in the mummi- 
fication of the umbilical cord. 

Pathological conditions capable of causing local death are 
usually such as interfere with the nutrition of the cells and tissues, 
and render the metabolic interchange between them and their 
surroundings impossible. The most common is some interruption 
of the blood supply; as thrombosis and embolism (both of which 
occlude the vascular lumen), rupture of the vessels, separation of 
the cells or tissues from their sources of supply (traumatic, or the 
Undermining of the skin in case of subcutaneous suppuration), or 
compression of the tissues which interferes with the entrance of 
blood to the part. If the blcod is unable to gain access to an 
organ or some portion of an organ, no more than mere microscopic 
parts of it can be maintained by the lymph ; with the exception of 
the cornea and the cardiac valves, for which the lymphatic fluid 
is the principal source of nutrition, no organ can withstand a pro- 
tracted interruption of its blood supply. This is especially true 
of gland cells; according to Litten two hours are sufficient after 
ligation of the renal arteries in rabbits to cause necrosis of the 
renal epithelium, even though after removal of the ligatures the 
circulation be re-established. Ehrlichand Briefer (cited from Birch 



178 Necrosis. 

Hirschfeld) observed a destruction of the gray matter as a result 
of withholding the blood supply for a single hour in case of the 
spinal cord. Interference with the venous outflow, if marked 
enough to cause stasis in the capillaries, is also followed by nu- 
tritive disturbances which terminate in gangrene. 

The vitality of the tissues may also be overcome by chemical 
and thermic influences producing coagulation or liquefaction of the 
proteids and thus either directly or indirectly rendering the pro- 
toplasm incapable of appropriating nutrition and giving off its 
metabolic products, as well as interfering with the interchange of 
gases (burns, freezing, poisons like the acids and alkalies, the 
digestive juices, bacterial poisons). Evaporation of moisture, as 
in case of evisceration, causes necrosis of the exposed organs partly 
by drying the protoplasm of the cells, partly by desiccating and 
stagnating the blood and lymph. [An important adjuvant cause 
of necrosis is also seen in the destruction of innervation of a part, 
as may be observed in the massive and fulminating necrotic changes 
met with in cases of lesions of the spinal cord at points of pressure 
below the level of the spinal injury, the well known gangrenous 
decubitus of such individuals. In some measure here, disregarding 
the important pressure factor, the necrosis may depend upon 
vascular changes due to the nervous lesion ; but there are reasons 
for believing a more direct cellular failure results as well, from 
the loss of the nervous trophic control.] 

As a general rule the occurrence of necrosis is to be attributed 
to a dual influence, the causative lesion having both a direct destruc- 
tive power upon the tissue and at the same time interfering with 
the circulation of its fluids. 

The characteristics of necrotic and dying parts vary with their 
structural peculiarities, the proportion of moisture in the. organ, 
the relation with the uninvolved parts, and external influences. 

Dense structures like bones and teeth are subject to a simple 
necrosis; these and the dense elastic tissues are extremely resistant 
to physical and chemical agencies, retaining long after complete 
death their form and general appearance as in life. Soft tissues 
also, like the epithelium of the stomach, if killed by poisons having 
disinfecting power (carbolic acid poisoning), may remain without 
material change, with but little alteration of form, just as ana- 
tomical specimens preserved in alcohol or formaldehyde solutions. 
In such instances the necrosis is primarily recognized by the reac- 
tion in the surrounding healthy structures im their effort to isolate 
the dead part {sequestration) . 



Dry Gangrene; Coagulation Necrosis. 179 

Necrosis with desiccation and shrinkage {mortificatio sicca, 
mummification, dry gangrene) results from deprivation of moisture 
by evaporation, compression, chemical action or prevention of 
the entrance of fluids to the part. A physiological prototype is ob- 
served in the shriveling of the umbilical cord which is converted 
in the course of a few days after birth into a dry brown parchment- 
like mass. On a small scale desiccation from loss of moisture may 
be seen in the formation of crusts (eschars) on the surface of 
wounds and ulcers, upon which usually the exuded fluid, pus, 
extravasated blood and a portion of the underlying tissue (cutis, 
mucous membrane) are dried up into brown or black crusts and 
scabs (eschars from caustics, scabs of wounds and ulcers). Mum- 
mification of deeper and more extensive type, changing the tissues 
into a wrinkled, brown or black, tough, leathery material, or into 
a completely dried hard mass, may affect the extremities, ears, 
feet, tail or quite frequently the skin, as the result of the action 
of poisons or complete exclusion of blood from the part involved, 
as in swine-erysipelas, ergotism or occlusion thrombosis. A com- 
mon example of this variety of necrosis is the leather-like mummi- 
fication which takes place in a dead foetus retained with its amnion 
in the uterus in case the amniotic fluid has all drained away or 
been absorbed, putrefaction being impossible because of the absence 
of the necessary bacteria, the foetus becoming a veritable mummy, 
enclosed and compressed in the uterine sac. 

Necrosis with coagulation, coagulation necrosis. Where 
necrosed tissue assumes the character of an albuminous coagulate, 
being changed into an elastic, dense, dull white, grayish yellow or 
yellow, and more or less dry mass, the type of destruction is 
described, following Weigert, under the term coagulation necrosis 
or sometimes caseation. This metamorphosis is peculiar in that 
the dead area does not seem diminished or shrunken and has ap- 
parently not suffered loss of its fluids, but rather tends to be some- 
what increased in volume, projecting slightly above the surround- 
ing structures. This swelling of the dead tissues depends upon 
the diffusion of lymph from the adjacent parts through the necrotic 
substance, saturating it. After this has taken place the coagulation 
occurs in the same way as in the formation of a blood clot, by the 
action of an enzyme which is either derived from the necrotic cells 
or originates from the primary cause of the necrosis. This variety 
of necrosis is often induced by certain infections germs (tubercle 
bacilli, necrosing bacilli, bacilli of swine plague) which seem to 



180 • Necrosis. 

give oft" a ferment into the tissues ; it is also frequently seen in 
infarcts caused by embolism and in new growths anaemic because 
of deprivation of their blood supply, in which necessarily it must 
be supposed that there is produced by the tissue disintegration 
some substance comparable to fibrin ferment. 

The saturation of a necrosed tissue by lymph is quite possible if 
evaporation is prevented (for this reason coagulation-necrosis is most 
commonly seen in parts enclosed from the air, internal organs and mucous 
membranes) ; in moist, necrotic tissue the blood circulation is, it is true, 
completely in abeyance, but the diffusion of the lymph and the immigra- 
tion of lymph corpuscles may be expected. 

[Many, among whom the editor would include himself, dif- 
ferentiate between coagulation-necrosis and caseation, regarding 
the latter as essentially a further destructive change, an advanced 
fatty degeneration of the necrotic substance. Where an area of 
coagulation necrosis, or what is practically the same thing, hyaline 
degeneration (at least some forms of the latter), is retained in the 
tissue and is not further disintegrated by liquefying processes 
it becomes the seat of fatty degeneration and is broken down into 
a fine detritus, oil droplets, and often contains crystals of cholesterin 
and fatty acids. When this is of advanced degree it is described 
under the name of caseation. Two varieties are commonly de- 
picted, dry and moist. Grossly a dry cheesy focus is usually de- 
fined, often encapsulated, whitish or yellowish in color, of a friable 
or crumbling consistence, reminding one much of dry "cottage 
cheese" ; and under the microscope appears as a uniformly granular 
mass, occasionally exhibiting a few persisting fragments of the 
original cellular elements, scattered oil droplets and crystals, and 
when stained selects diffusely the acid stains like eosin. A moist 
cheesy focus (which may represent an area from which the moisture 
has not been absorbed or which may be determined from a dry 
focus by imbibition of lymph and by liquefaction of its own sub- 
stance) is usually not so clearly defined as a dry caseated area, is 
paler in color, softer in consistence (pasty or mushy, like "cottage 
cheese" mixed with milk) ; and microscopically presents the same 
appearance as mentioned for the dry variety with the additional 
feature that usually the fat globules and crystals are more numer- 
ous. Caseation is especially common in tuberculous and syphilitic 
lesions, a form of coagulation (a variety of infectious hyalin de- 
generation) preceding the fatty change ; it however may be met 
as a late change in a variety of lesions, as in atheroma, in the mti- 



Liquefaction-Necrosis ; Moist Gangrene. 181 

tents of a "residual abscess," etc. The moist cheesy matter is the 
well known "pyoid" material of "cold abscesses/' In dry casea- 
tion calcification is apt to occur as a terminal change.] 

Necrosis with softening, liquefaction-necrosis. Necrosing tissues 
which are poor in coagn table albuminates but rich in fat and fatty 
substances, and which contain considerable fluid or are in position 
to obtain it from the entrance of lymph, usually break down into a 
soft pulpy mass or into a milk-like emulsion. The process may 
occur as a primary one, as in the brain and cord, because of the 
large amount of myelin contained by these parts (as also 
seen in infarcts and hemorrhagic effusions) ; or it may occur 
as a secondary change where an originally coagulated necrotic sub- 
stance becomes macerated after fatty degeneration or saturation 
with serous fluid, or is softened by the liquefying products of 
various bacteria (soft caseation, purulent softening). [The type 
of liquefaction here described is essentially the same mentioned 
by the editor under the name of moist caseation in the last note. 
There is a form of liquefaction however in which the fatty elements 
mentioned by the author are absent or at least not important, the 
necrotic tissues becoming converted into a clear, watery fluid. This 
resultant fluid may in a greater or less measure be the product of 
actual conversion of the solid substance into liquid ; in part it is 
made up of lymph, which has penetrated the part. The disappear- 
ance of the solid substance may be a mere solution of the soluble 
portions in the absorbed fluid, but in addition the insoluble portions 
may be rendered soluble or changed into fluid by the influence of 
poisons (often bacterial), heat or cold or by enzymes originating 
in the necrotic tissue itself or generated by the surrounding living 
cells or by microorganisms present in the mass. Such material 
is apt to be removed from the affected part, usually by absorption, 
or may be retained within a capsule as a cyst.] 

Necrosis with putrefaction, moist or putrid necrosis, gangrene 
(17 ydyypaiva ) , sphacelus (6 o-<t>dK€\os from <r0dseu>, to kill), phagedena 
(v <f>ay48au>a). When necrotic tissue rich in fluid is open to access 
of putrefactive bacteria a putrid decomposition sets in precisely as 
in case of a piece of meat or a cadaver. The gangrenous area is 
soft, pultaceous, filthy, dark brown to green or dark red in color, 
stinking and permeated by putrid gases. The putrefactive bacteria 
gain entrance from the surrounding air to the softened part through 
lesions (from wounds or ulcers) of its protective covering (epi- 
derm, skin) or from the canals lined by mucous membrane, upon 



1 82 



Necrosis. 



the surfaces of which there is apparently always present a rich 
variety of bacteria (pharynx, stomach and intestines). The 
putrefactive germs may be carried from such situations by the 
lymphatic and blood streams into the internal organs, where new 
foci of the putrefying process result from embolism. Tissues the 
seat of marked hemorrhagic infiltration and those with large lymph 
spaces, are especially likely to become gangrenous, the stagnating 
blood and rich supply of moisture favoring the multiplication of 
the putrefactive organisms. The discolored liquid of the decom- 
posing part is known as putrid ichor. 




Fig. 20. 



Microscopic section through a necrotic area in liver of cow; the border of 
the coagulated necrotic material close to the normal tissue showing a 
zone of cellular infiltration. 



Microscopically, the principal change exhibited by necrosing tissues 
is the disappearance of the nuclei, shown especially by their partial or 
complete loss of the staining quality with the ordinary nuclear staining 
reagents (haematoxylin, carmine stains). Sections of normal tissues 
present their cells and nuclei stained with clear definition and distinct 
color ; necrotic portions look as though they were without nuclei, and 
either refuse to take the stain or only assume a faint diffuse coloration. 
The nuclear changes ma}* consist of a loss of a definite outline, accumu- 



Symptoms of Necrosis. 183 

lation of the chromatin in fragments or clumps of irregular size and 
a variety of angular or globular shapes in the nuclear stroma along the 
periphery (karyorrhexis), or its escape into the cytoplasm {pyknosis of 
Schwann and Albrecht), or its complete dissolution (karyolysis of Klebs). 
Besides this fragmentation of the nuclei, displacement and solution of their 
chromatin, there are also to be observed changes in the cellular proto- 
plasm and in the intercellular substance, resulting in the loss of specific 
structure. The cell protoplasm and supporting tissue are changed into 
a turbid, lumpy, more or less homogeneous mass, in which the individual 
cells can no longer be recognized. In case lymph diffusion in the 
necrosed tissue follows and coagulation occurs, the dead area seems to 
be filled with apparently swollen, shining, strongly refractile, fibrin-like 
masses of transudate (fibrinoid of Albrecht and Schwann) of lumpy, 
trabecular or reticulate appearance. In necrosis with softening the de- 
structive change is usually recognized by the fat droplets (fatty detritus) ; 
and the ichor of gangrenous parts shows, in addition to shreds of the 
various tissues, the remnants of the liquefied red blood cells in the form 
of yellow and dark brown granules and clumps of blood pigment, and 
sometimes such solid decomposition products as leucin, tyrosin, margarin 
and triple phosphates, together with an enormous number of putrefactive 
microorganisms. 

Symptoms of necrosis. Local death of tissues causes their com- 
plete loss of functional ability. When the necrosed focus is of 
small size and situated in the midst of healthy functionating tissue 
of the same type and having the same character of activities, 
there are often no symptoms, as in case of anaemic infarcts of the 
kidney and spleen. The distribution and production of heat ceases 
in the necrosed part with the cessation of the blood supply ; gross 
areas of gangrene on the periphery of the body, as the skin, ears 
or extremities, feeling cold. Because of the coincident death of 
the sensory nerves within the gangrenous area the latter is itself 
analgesic, although the inflammatory reaction at the periphery 
causes sensations of pain. Gangrene in its inception is further 
recognizable in parts of the body exposed to view by the dark 
brown, dirty dark red to dark green discoloration, by the desic- 
cation, or by its putrid odor. " In this latter form, that is, gangrene, 
the parts assume a doughy, flabby consistence ; and if the gases 
cannot easily escape and accumulate deep in the meshes of the 
tissue there may be felt by light palpation a crackling (crepitation) 
of the breaking or displaced gas bubbles, The presence of the 
gases gives the putrefying tissue a bloated, spongy appearance, the 
cut surface full of small holes (gangrenous emphysema) ; together 
with the ichorous fluid these gases often accumulate under the 
epidermis in cutaneous gangrene and cause the formation of gan- 
grenous blebs. 



184 Necrosis. 

Terminations. Dead tissue acts upon the surrounding healthy 
structures as a foreign body, causing both mechanical and chemical 
irritation ; in consequence of which an inflammatory reaction is 
uniformly established in the adjacent healthy tissues. At the 
periphery of the necrotic part there may be observed an inflam- 
matory zone marked by greater or less inflammatory hyperemia 
and accumulation of leucocytes. From the action of the fluid 
exudates penetrating the dead tissue and of the immigrated cells 
removing the necrotic substance, partly by liquefaction and partly 
by phagocytosis, necrosed parts of small size may be gradually 
absorbed, especially foci softened down into detritus and small 
infarcts. At the site of the necrosis there is then left a space, a 
defect, which is later filled in by proliferation of the surrounding 
tissue or by inflammatory scar formation. Larger necrotic areas, 
or such as apparently cannot be softened (mummified and coagu- 
lated portions) resist absorption; these may be circumscribed by 
the inflammation, encapsulated or completely separated from the 
rest of the body {demarcation, demarcating inflammation, sequestra- 
tion or circumscribed necrosis). In this way while the invading 
mass of leucocytes and other exudates are softening down the tissue 
at its borders there is also proceeding an inflammatory prolifera- 
tion of connective tissue and blood vessels (fibroblasts, angioplasty 
and blood vessel buds) to the formation of a protective wall. If 
the dead material be situated at the surface of the skin or mucous 
membrane it may be sloughed off (cutaneous slough), and the 
defect repaired either by subsequent proliferation of the adjacent 
tissue or by cicatrization. Necrotic parts situated deeply in the 
body are surrounded by the demarcating tissues and come to be 
enclosed in a dense capsule of connective tissue. Dead fragments 
of bone separated from their circulatory supply (bone splinters) 
are enclosed by an osteoplastic proliferation of the bone marrow 
and periosteum and thus isolated as sequestra. 

In case the gangrenous foci contain substances of toxic nature 
the necrosis may assume a progressive character from the con- 
vection of the toxic products of disintegration and putrefactive 
bacteria by the invading leucocytes and lymph stream to other 
parts. When the process is reproduced in the immediate vicinity 
of the original focus it is spoken of as progressive necrosis or 
gangrene; when the putrefactive organisms are carried in the blood 
to distant parts, causing synchronously the same processes in the 
latter, these new foci are spoken of as secondary, metastatic gan- 



Atrophy. 185 

grenous foci, embolic gangrene. A general putrid intoxication 
{sapranhia, from <xair P bs , decomposed, and al/xa , blood; mixed 
septic intoxication) may result from the toxines of putrefying bac- 
teria in the blood and the products of decomposition absorbed from 
a gangrenous focus ; this is likely to run a fatal course with 
symptoms of fever, collapse, marked cerebral disturbances, myo- 
cardial degeneration, tendency to multiple haemorrhage, etc. The 
poisons arising from putrefying matter or generated by special 
putrefactive bacteria have haemolytic properties and are paralyzant 
to the cardiac ganglia or central nervous system. 

Examples of this are frequently afforded in case of wounds of 
the skin which favor putrid suppuration of the underlying tissue 
(tooth bites, punctured wounds from stable forks), in putrefaction 
of the retained placenta and gangrene of the uterus, in intestinal 
strangulation, deglutition pneumonia and in escape of the contents 
of the stomach and intestine in consequence of perforation of the 
walls of these organs. 

Atrophy. 

The term atrophy is employed to indicate a diminution in volume 
of an organ or tissue without essential alteration in its structure 
and chemical composition. It involves a reduction in size of the 
cells and tissues {simple atrophy) ; but this often proceeds to an 
extent that actual loss of the cells results from their complete re- 
gression (numerical atrophy). The name of the process, derived 
from Tp6<pos, nourishment, and a privative, means, precisely, loss of 
nutrition, and is used because atrophy in the main is due to in- 
sufficient nutrition. This latter factor may depend upon the fact 
that the cells actually do not receive sufficient nutriment (passive 
atrophy) or that they lack the ability to appropriate that which is 
offered them (active atrophy), both of which conditions may syn- 
chronously prevail and are impossible of definite separation in all 
cases. 

Atrophy of organs and their elements may in some cases be a 
physiological phenomenon, a part of the cycle of their development 
and natural wearing out. Certain structures developed in 
embryonic life undergo retrogression even before birth or soon 
after, as the Wolffian bodies, the ductus Botalli and ductus Arantii, 
the umbilical vessels and the thymus gland. In the period of most 
active growth the milk teeth disappear after atrophy of the dental 
pulp. Throughout the entire lifetime there is a succession of atro- 



1 86 Retrogressive Processes. 

phy of worn out, aged cells with replacement by new and func- 
tionally capable cells, as the protective epithelial cells, glandular 
cells or the blood corpuscles. Dependent largely upon inherited 
capacity of length of life peculiar to the individual, sooner or later 
a retardation in the cytogenic energy makes its appearance as a 
characteristic of old age ; this physiological loss of tissue-forming 
power leading to shrinkage of the affected parts is termed senile 
atrophy. This is particularly noticeable in the sexual glands. The 
ovaries dwindle after the discharge of the ova generated in early 
life ; no more follicles mature ; the connective tissue stroma and 
tunica albuginea become dense and the organs assume a cicatricial 
appearance. The testicular epithelium leaves off its spermatogenic 
activity, becomes lower and smaller. In the same way in the lym- 
phatic structures, the spleen, lymph nodes and bone marrow, the 
ability for cellular proliferation is curtailed and hand in hand there 
occurs reduction in the formation of blood corpuscles. Even the 
skeletal system undergoes considerable atrophy in age, the bones be- 
coming more porous and brittle and lose sensibly in weight; a pro- 
gressive thinning of the bone trabecular is especially notable, probably 
caused by increase in a special group of cells (giant cells or osteo- 
clasts ; bareov, bone, and nXaaaeiv, to break) which are concerned 
in the absorption of calcareous matter. The ganglion cells of the 
brain become reduced in size. At least in part senile atrophy is due 
to a physical wearing out, as when certain structures become dilated 
from mere loss of elastic resistive power (elastic fibres which have 
lost their tone like a worn out rubber band). 

The following pathological conditions productive of atrophy are 
to be considered. 

i. Lack of use of organs. Repeated physiological stimula- 
tion is essential for the preservation of all cells, keeping cellular 
function active by constant use. Cessation of this type of stimula- 
tion and the resultant failure of function are productive of atrophy 
{atrophy from inactivity). For instance, prolonged fixation of a 
limb by skillful bandaging or the immobility from ankylosis of a 
joint may be followed by atrophy of the muscles and bones of the 
part. As the stimuli are conveyed by the nerve tracts it must be 
evident that disturbances in the conductivity of the nerves or loss 
of nervous impulse are especially apt to occasion atrophy {neuro- 
pathic atrophy). This may be observed in palsies, as those of the 
hind quarters (frequently seen in dogs from injuries to the spinal 
cord), in which the musculature of the hind legs may be reduced a 



Atrophy. 187 

third or half in volume from the important loss in size and number 
of the muscular fibres. Vice versa, if an organ to which they are 
distributed undergo atrophy or be destroyed, the nerves become 
atrophic ; the optic nerve atrophies completely in protracted disease 
or destruction of its eye. 

2. Compression. Continual pressure upon a tissue inter- 
feres with growth, hinders the blood supply to it and its lymph 
circulation, and directly causes diminution in the size of its cells. 
Pressure atrophy is conspicuous wherever unavoidable, protracted 
and gradually increasing compression of the tissues obtains. The 
renal parenchyma becomes atrophic and eventually as thin as paper 
from interference with the urinary discharge from the pelvis of the 
kidney; nodular tumors produce depressions in the tissues in con- 
tact with them; an iron cavesson makes a deep groove in the nasal 
bones ; a hoof corn (growth of the horny hoof) causes a corre- 
sponding pressure wear on the hoof bone. Many facial malforma- 
tions may be explained as the result of amniotic bands being wound 
about the jaws in the process of development, interfering with the 
further growth of the upper and lower processes of the first visceral 
arch. Cysticerci (echinococcus, ccenurus) in their growth cause 
pressure atrophy of the substance of the organ in which they are 
lodged (ccenurus upon the brain and skull). Even the cellular and 
fibrillar connective tissue masses found in chronic inflammation as 
well as merely a marked engorgement of the blood vessels may 
serve as compressing influences upon the surrounding elements ; the 
liver cells atrophy in chronic inflammation of the hepatic connective 
tissue and in chronic passive congestion. 

3. Deficient Nutrition. A diminution of nutritive supply 
obviously must occasion atrophy (atrophy of inanition) , as the 
tissues can only retain their dimensions and energy of growth when 
proper pabulum is provided them from the blood. Insufficient 
nutrition in diseases of the digestive organs which render difficult 
the ingestion of food or absorbtion of nutrition, or deficiency of 
local blood supply, allow the cells to waste away. In starvation, the 
fat of the body is lost (91 to 93 per cent, of the loss in weight) ; and 
the musculature (42 per cent, according to Samuel) and the cells of 
various organs become smaller. According to Manawein in rabbits 
the cells of the liver, which average 22.3 micromillimeters in meas- 
urement, are reduced to 8.9 micromillimeters in diameter. The 
loss of nutrition is an associated factor in pressure atrophy and 
neuropathic atrophy. 



i88 



Retrogressive Processes. 



The loss of volume of the cells in atrophic conditions consists in 
part in decrease of their so-called paraplastic substances, partly in 
loss of their actively functionating constituents (Ribbert). The 
former, including the stored-up nutrient matter (fat, glycogen) and 
the cellular secretory products (mucin), are generally used up 
without chance of replacement from the blood supply or from the 
protoplasm ; the above-mentioned diminution of size of the liver 
cells, for example, resulting, or of fat cells which after loss of their 







Fig. 21. 

Fatty infiltration of the sural muscles in pseudohypertrophic muscular atrophy 

X 220. (After Thoma.) 



fat are found shrunken into simple connective tissue spindle cells. 
The functional substance, as the contractile substance of muscle 
cells, undergoes metabolic alterations resulting in diminution of 
its bulk. It is difficult to make out how intercellular substances 
come to undergo the observed solution and removal, as it cannot 
be here assumed that it is simply carried off by the lymph, the 
appearance of giant cells indicating clearly that the processes opera- 
tive are of complicated nature. In the bone marrow the presence 
and increase of these elements seem to be related with the removal 



Atrophy. 189 

of the hard bone substance, the calcified lamellae being literally 
gnawed away by them. In addition muscle undergoing atrophy is 
apt to show proliferation of the muscle nuclei, the sarcolemma 
sheath often being full of nuclei and giving the impression of multi- 
plication from lack of tissue pressure (lack of tissue tension) within 
the empty sheath, as an associated phenomenon. This same ten- 
dency to fill up spaces may also be observed in the fat cells, in 
which, after the fat has been used up, there often accumulates a 
watery or mucinous fluid, giving the adipose tissue a loose gelatin- 
ous character {dropsical fat atrophy, often met in old horses in the 
epicardium). Sometimes succeeding an atrophy in one tissue a 
hypertrophy may take place in another, adjacent tissue ; as when in 
atrophy of muscular fibres the resulting space comes to be occupied 
by proliferation of fat cells {atrophia musculorum lipomatosa) . 

The deposition of the brownish pigment granules accompanying vari- 
ous atrophies (muscle, heart, liver, ganglionic nervous cells) is as yet 
not satisfactorily explained. [There is no doubt, however, that in most 
cases at least, this pigment is of hsemic derivation, although the substance 
has been in some degree modified by cellular metabolism, and may there- 
fore be spoken of as autochthonous in conformity with its usual classifi- 
cation. It is a common feature of atrophic parts, as might well be expected, 
both from the importance of poor blood circulation as a causative factor 
and also from the diminished support afforded the capillary walls of 
the wasted tissue, that some degree of passive hyperemia should prevail; 
and it may be noted that the degree of this pigmentary change is usually 
in direct relation with the degree of' such congestion.] 

Anatomically atrophic parts are usually characterized by dimin- 
ution of volume, poor blood supply [poor circulation, not neces- 
sarily poverty of amount of blood present, however], loss of 
their adipose tissue, by a tough, dry appearance and by the assump- 
tion of a peculiar grayish tint sometimes approaching a brown color. 
The general bulk of the part may, however, be maintained by the 
compensatory occupation of the space caused by the wasting of 
its proper constituents by fat or connective tissue. Organs which, 
because of their situation or the density of their peripheral structure, 
are incapable of diminution may, however, manifest the presence 
of atrophy by loss of weight, as the bones and lungs (osteoporosis 
and emphysema*). 

Atrophy invariably causes loss of function. Atrophic muscles 
eventually are incapable of motion; glands secrete less efficiently; 
bones become brittle; nervous structures lose their irritability ami 

♦For details of these conditions «•!'. Kid. Lehrb. <i. patltol. Anatomie </ 
ITausticrc, II. Aufl., Enkc, Stuttgart, 1902, 



190 Retrogressive Processes. 

power of nervous conduction. Its consequence to the life of the 
individual varies with the importance of the affected organ. 
Atrophy of one of the bilaterally situated organs may be corrected 
(compensated) by hypertrophy of the other, as in atrophy of one 
kidney or of one lobe of the thyroid gland. 

General atrophy of the organs involving the musculature, the 
general fat of the body and the glands, associated with anaemia and 
resulting from general disturbances of nutrition, is known as 
cachexia (^ Kax^ia, a bad condition; from -fj g£«, condition, and 
KaKbs , bad), or when a phenomenon of old age, as marasmus 
{txapaivu, to fade). 

Albuminous Degeneration or Cloudy Swelling. 

Abnormal metabolic processes and lesions of the cellular proto- 
plasm may often manifest themselves by increase of cellular volume 
and the appearance of densely packed fine dust-like albuminous 
particles in the cytoplasm, with consequent obscuration of the 
nucleus and the production of a turbidity in the cell substance. By 
treatment Avith acetic acid (two per cent.) or potassium hydrate 
(one per cent.) these granules are dissolved and the nucleus be- 
comes clearly visible. Their solution in excess of acetic acid, brown 
coloration with iodine and acquirement of a bright yellow tint 
with nitric acid (xanthoprotein reaction) indicate the albuminous 
character of these granules. Various cells, particularly those of 
glandular type, are normally granular, but as a rule the nucleus is 
easily made out and the cells are of their fixed size and shape ; 
while the pathological granulation is distinguished by the swelling 
and irregularity of outline of the cells and by the loss of their nor- 
mal structural characteristics. In muscle fibres, which show the 
change particularly well, the transverse striations are lost and the 
myoplasm is filled with fine dust-like granules reminding one of 
particles of India ink; hepatic and renal epithelium looks swollen, 
expanded beyond the physiological limits, the former no longer 
arranged in columns (spoken of as dissociation by Browicz), the 
renal cells narrowing the uriniferous tubules to occlusion. 

In sections this turbidity is usually not easily observed, being cleared 
up by the processes of preparation (alcohol, xylol, etc.). The structural 
lesion may also be inferred in cloudy swollen cells by the disappearance 
of Altmann's granules (bioblasts). (Altmann claimed that in the cells 
of the liver and kidneys there are fine granules around the nucleus ar- 
ranged in regular rows, which could be uniformly demonstrated by certain 
staining methods. In cloudy swelling these granules are no longer recog- 
nizable.) 



Cloudy Swelling. 



191 



This process, known as cloudy swelling, albuminous turbidity 
or albuminous degeneration, first described by Virchow, occurs 
principally as a result of toxic influences, both definite poisons 
(phosphorus, arsenic) and the toxines of infectious processes 
(diphtheria, septicaemia), and, too, from autointoxication from in- 
flammatory changes. It may be regarded as an expression of dis- 
turbance of metabolism caused by such toxic action, with impair- 



SL}i. 




Fig". 22. 
A, Cloudy swelling-; B, Complete degener- 
ation of striated muscle fibres. In 
B the middle fibre is normal, that to 
the left in early, and that to the 
right in advanced degeneration; 
X 250. (After Perls.) 




Fig 23. 
Muscle of horse (hiemoglobin- 
semia, 7 hours after the at- 
tack); a, normal fibre; b, tur- 
bid and granular fibre; c, 
hyaline degenerated fibre. 
(After Zschokke.) 



ment of the elaboration of the nutrient matter appropriated by 
the cells. Either the protoplasm is incapable of assimilating the 
albuminous bodies brought to it and they therefore accumulate in 
undissolved condition ; or, as Virchow assumed, the cell is in a 
condition of metabolic irritation in which there occurs an ex- 
cessive separation of its albumens; or it is a beginning cellular dis- 
integration with formation of modified albumens in the tissue. 
which are with difficulty soluble. [To a certain extent it seems 



192 



Retrogressive Processes. 



probable, too, that the swelling of the cells is referable to an ex- 
cessive presence of fluid, a cellular dropsy.] 

Functional disturbances are occasioned by cloudy swelling, well 
seen in the diminished contractile power in muscle. It is a repara- 
ble process (recognizable in renal disease) provided the toxic sub- 
stances which occasioned the protoplasmic fault are removed. 

Anatomically organs which are affected by albuminous degenera- 
tion are usually less transparent than normally because of the 
turbidity of their cellular constituents, are more or less grayish or 
clay-colored, dry, friable, soft, and look as if they had been scalded 
or cooked. 

The condition under discussion is very distinctly met in the psoas and 
thigh muscles of the horse in myopathic hsemoglobinuria, in the myocar- 
dium in various infectious diseases (as pleuropnuemonia, tetanus), in the 
liver and kidneys in phosphorus poisoning. 

The Fatty Changes. 

The presence of fat in the tissues is a physiological condition 
depending in variable measure upon the nutrition brought about by 
storage of the fat directly derived from the food or formed within 



m 

m 



a 




Fig. 24. 



Fatty infiltration of liver cells ; a. normal hepatic cell : b-e, various stages of 
development of fatty infiltration; X 600. (After Thoma.) 

the cells from the carbohydrates and albumens. Deposition of fat is 
especially seen in the subcutaneous, submucous and subserous con- 
nective tissue, in intermuscular septa and in the glandular epithelium 
of the liver, mammary gland, sebaceous glands, and also in dogs 
and cats in the renal epithelium. The affected cells show the 
presence of fat as either large or small droplets ; and may either 
have normal nuclei, with the cellular volume varying in size with the 
amount of fat present (fat cells, fatty infiltration), or structural 
changes are evident, which indicate a cellular destruction (fatty 
degeneration, fatty metamorphosis). In this latter case the fat is 
frequently found in innumerable minute, highly retractile globules. 



The Fatty Changes. 



193 



the nuclei are obscured or destroyed, and the outlines of the cells 
irregular. The difference from albuminous granules may be 
recognized in teased preparations by the fact that the fat droplets 
are not affected by acetic acid and alkalies, and in microscopic 
sections, which have been carried through alcohol and ether, 
chloroform or xylol, by the removal of the fat by these reagents, 
the places where it was present in the protoplasm consequently ap- 
pearing as vacuoles (small holes or spaces — foam structure of the 




Fig. 25. 

Nodular fatty liver of dog; portion of a section under low magnification. (After 

Rauscher.) 



cells). An excellent method of demonstrating the fat microscopic- 
ally is by staining with Sudan III (an aniline dye), which may 
be employed in teased tissue or frozen sections after hardening 
with formol, but not after the use of fat solvent reagents, the fat 
droplets being tinged an orange yellow color by the dye. Fat ma) 
also be fixed by osmic acid, which makes it black and renders it 
insoluble in alcohol, ether and chloroform (it is. however, still 
soluble in benzine, toluol and xylol — Dink). 

Fatty degeneration may be well seen in muscle fibres, in which 



194 



Retrogressive Processes. 



the transverse striae are lost and the substance found thickly beset 
by fine fat globules. Complete cellular destruction by fatty de- 
generation is shown by the fact that finally nothing of the cell 





; 



Fig. 26. 

Fat crystals (so-called margaric acid needles); X 250. (After Perls.) 

protoplasm remains but a mass of fat globules {fatty granular mass, 
fatty detritus, from deterere, to disintegrate; [also often known 
as compound granule cells]). Where the fatty metamorphosis 
is further advanced crystallization of part of the fat in the 




Fig. 27. 

Cholesterin plates (after Perls); X 250, 



The Fatty Changes. 



195 



pulpy fatty remnants of the tissue may take place ; these fat 
crystals form clusters of needles, apparently not rigid, but seem- 
ingly easily bent (margaric acid crystals), or may appear in the 
form of thin plates with their corners broken out and superimposed 
upon one another in a step-like fashion (cholesterin plates, turning 
red with the addition of sulphuric acid, and upon further addition 
of iodine taking a violet or blue color). 

The difference between fatty infiltration and fatty degeneration 
as well as their genesis (whether the fat present in the cells is 
derived from the fat brought to them or is produced by a local 
splitting process) is in most cases impossible of determination; 
sometimes even the microscopic picture is confused and even in 
undoubted infiltration the cellular protoplasm may exhibit appear- 
ances of alteration. Moreover, it is often impossible to tell whether 
the destruction of the cell was brought about by the fat accumula- 
tion, or because of some special affection of the cell itself and the 
fat in the latter case merely an associated or resultant phenomenon 
of the destructive change. 
Theoretically a difference 
may exist in the proportion 
of moisture retained in the 
tissue. In fatty infiltration 
the water is forced out of the 
tissue and may fall to below 
50 per cent. ; while in fatty 
degeneration the proportion 
of water in the tissue (75 to 
78 per cent.) remains normal 
(Perls). In fatty infiltration 
the addition of fat to a liver 
may sometimes be so marked 
that it exceeds 40 per cent. ; 

while the fatty degenerated organ scarcely ever contains more tHin 
8 per cent. (Perls). 

It remains, therefore, a disputed question whether the fat is 
formed by cellular function or whether it is entirely derived from 
the food and is hence only transported fat. Undoubtedly the supply 
of fat or carbohydrates plays an important part both in physiological 
and pathological fatty degeneration. The studies of Rosen fold 
indicate that in experimental fatty degeneration of the liver, the 
fat of this organ is not necessarily produced therein, but is 




Fatty degeneration of liver cells ; a, liver 
cell of a man dead from acute phos- 
phorus poisoning, in physiological salt 
solution ; b, the same after removal 
of the fat by alcohol and oil of 
origanum ; c, fatty degenerated liver 
cell of a woman dead from septico- 
pyemia, in physiological salt solu- 
tion; X 600. (After Thoma.) 



196 Retrogressive Processes. 

brought to the liver (via blood or lymph) after removal from 
other parts of the body (subcutaneous tissue), because when 
sheep-fat was injected subcutaneously it later appeared in the liver 
and formed the principal part of the fat of this organ. 

Outside the body fat may be produced from proteid, as shown 
by the investigations of Voit, Pettenkofer and Virchow. Examples 
are met with in the formation of a peculiar wax-like substance 
known as adipocere (adeps, fat, and cera, wax) in corpses, a fatty 
change taking place in those parts of the body lying in water or 
moist earth, as the result of which they acquire a spermaceti-like 
nature ; in fatty transformation of fat-free pulmonary tissue pre- 
served in water (E. Voit) ; in the possibility of fattening animals on 
purely proteid diet (Voit, Pettenkofer, Cremer). Pfliiger doubts, 
however, whether in the body fat is formed from proteid decomposi- 
tion. [The prevailing opinion is that direct transformation of pro- 
teid into fat does not occur, and that when this is apparently the 
case, as in the author's examples, there are intervening stages or spe- 
cial causes. Thus glycogen may be formed from proteid by metabolic 
changes and the possibility of fat production from this polysac- 
charid must be apparent ; or bacterial agency may be assumed in 
many instances. The substance of the bacteria may here be held 
a possible source of fat, and, too, their enzymes seem capable of 
splitting the proteid molecule, with possible ultimate fat formation. 
In one of these indirect modes it may be accepted that fat may be 
produced from proteid ; and to whatever degree these may apply to 
pathological changes in the living body it may be held that the fat 
in question may have had an original proteid origin. 

There is another possibility, related, it is true, with the following 
paragraph, but not distinctly indicated by Professor Kitt, which 
should be held as a possible explanation of the appearance of fat 
in fatty degenerated cells. Fat combined in the general protoplas- 
mic molecule may exist without being visible ; in case of disintegra- 
tion of the protoplasm this combined fat may be set free and be- 
come apparent. 

And at last from the standpoint of application to the clinical 
importance of the case, the really important point is not so much 
the discovery of the fat in the cell as it is the fact that the cell 
is undergoing a disintegrating process — and it is this which should 
always be kept in mind. Whatever be the theoretical claims for 
considering fatty infiltration and fatty metamorphosis together, 
the student should, for practical purposes, hold them clearly sep- 



The Fatty Changes. 197 

arated, infiltration as a relatively unimportant accumulation of fat 
from deposition, the fatty degeneration as a serious and eventually 
fatal process of disintegration with the appearance of fat, for one 
reason or another, in the degenerative protoplasm.] 

Ribbert declares that the pathological essence of fatty metamor- 
phosis is to be sought in the fact that the cells have undergone a 
retrograde change which renders them incapable of further dealing 
with the fat obtained from the blood, or that the cells actually 
synthesize the carbohydrates, and possibly the albumen appropriated 
from the blood, into fat, but cannot further deal with it, so that it 
is not oxidized and remains unchanged. According to this view the 
process is essentially one of disturbance of metabolism. The rela- 
tion between pathological fatty degeneration and metabolic faults 
is apparent, moreover, in the fact that it is especially likely to occur 
whenever the processes of oxidation are impaired in the body ; as 
in all disturbances accompanied by diminution in the red cells or 
in the haemoglobin of the blood, the means of oxygen distribution ; 
in general oligaemia caused by blood loss or affections of the alimen- 
tary tract ; in parasitic anaemias and in local anaemias ; in the fatty 
changes commonly resulting from imperfect vascularization and 
its accompanying local anaemia, particularly in rapidly growing 
tumors (carcinoma and sarcoma). Destruction of the erythrocytes 
and consequent diminution of the oxygen content of the blood, or, 
too, reduction in oxygen appropriation by the cells of a tissue be- 
cause of some alteration, may result from various toxic causes ; 
in these there arise, as important or associated lesions, fatty de- 
generation of the liver, kidneys, myocardium and other structures. 
It sets in with especial intensity and rapidity in phosphorus poison- 
ing, in which the liver is usually diffusely degenerated (phosphorus 
liver), in poisoning with arsenic, antimony, iodoform, phenol and 
in severe biliary intoxication of the blood (icterus). Bacterial 
toxines in the circulating blood in infectious diseases likewise occa- 
sion this metamorphosis. 

In regard to excess of fat in the tissue there docs not obtain 
any sharp limit between the physiological and pathological grades. 
"Marked general increase of adipose cells gives rise to a condition 
of corpulence or obesity (ob-cderc, to eat up), adipositas (adeps, 
fat) or lipomatosis ( \Itos, fat). Peculiarities of metabolism here, 
too, are essential basic factors, occurring in individuals both as 
congenital and acquired faults and arising after atrophy of the 
sexual glands or after castration. 



198 Retrogressive Processes. 

According to the experiments of Lowy and Richter,* there is con- 
siderable diminution in oxidation power connected with atrophy of the 
sexual glands. The authors found that in bitches, seven weeks after 
castration, the consumption of oxygen for each kilo, of body-weight was 
reduced about twenty per cent., and in spite of increase in body weight 
the total gas interchange decreased about nine per cent., a reduction 
followed up to about twelve months after operation ; in castration of 
males the diminution of gas exchange set in within but a few days. 
Inasmuch as this loss is- immediately removed by feeding ovariin to 
females and spermin and didymin to males after castration, and the 
same disturbances recur after stopping the administration of these sub- 
stances, it may be assumed that the sexual glands possess a chemical 
function in connection with metabolism. 

When obesity is referable to an especially rich supply of fat 
or fat-forming substances animals are said to be ''fattened" (dietary 
obesity, obesitas ex alimcntis) . It is well known that this is favored 
by repeated venesection ; the lowering of gaseous exchange from 
the removal of blood corpuscles may be a factor in this case. 

Local accumulations of fat in the vicinity of atrophic tissues 
are found, filling in the spaces left through the atrophy, as in atrophy 
of the muscles and kidneys (fat hypertrophy ex vacuo). 

[xAmatomically a part, as the liver, which is the seat of fatty 
infiltration, is apt to be of a light yellowish color, enlarged, its 
capsule tense and smooth and the margins tending to be rounded 
when the amount of fat deposited is great. It cuts with lessened 
resistance and the cut surface and the section knife are greasy.] 
A pathological obesity (which is progressive) is anatomically 
recognizable by the increase of the panniculus adiposus in the 
subcutaneous tissue, the peritoneum, mesentery, epicardium and as 
a diffuse extension through the tissues, as the muscles. 

Fatty degeneration is characterized by a dull yellow, ochre or 
clay-colored appearance of the organs, sometimes by distinct in- 
crease of the volume [typically the reserve because of the cellular 
destruction which is taking place] , a pasty, doughy consistence or 
friability, a greasy sensation given to the hand, and a greasy de- 
posit on the knife used for section of the organ, and by indistinct 
structural marking of the part. Sometimes the discoloration is in 
streaks or flecks. The process may be associated with cloudy 
swelling, when the parts look as if they had been cooked [and are 
apt to be of increased volume from the latter degenerative change] . 

The pathological significance of fatty infiltration and of fatty 
degeneration depends upon the extent and intensity of the process 

*Cited from Herm. Hahn. Anat. u. phys. Folgeerscliem. d. Kastration. Sitzungs- 
ber. d. Gesellsch. f. Morph. u. Phys. in Munchen, 1902, XVIII, Heft 1. 



Hyaline Degeneration. 199 

and upon the relative importance of the affected tissues. Pre- 
cisely in the same way that fat in the adipose connective tissue 
cells is a reserve and may be removed from these cells, there is 
possible a recovery from fatty infiltration in case of these or any 
other fat containing element, provided the cells are otherwise 
healthy. Even fatty degeneration is recoverable to the extent 
that replacement of loss in affected cells occurs from remaining 
normal cells or nuclei (mitotic nuclear figures have been found in 
fatty degenerated cells (Ribbert), and the ordinary recovery from 
the infectious diseases in which muscular and hepatic fatty meta- 
morphosis is apt to occur would substantiate this view). The 
massive increase of adipose tissue in the body may be harmful to 
the rest of the tissue elements from the mechanical effects of dimin- 
ishing space and compressing the cells against each other, as in 
the heart, where in case of excessive fatty infiltration the fat pene- 
trates between the cardiac muscle fibers. Liver cells, which are 
the seat of marked fatty infiltration and consequent enlargement, 
compress the capillaries distributed between the cell columns, and 
in this way give rise to anaemia and its results. Both cells and 
tissues are rendered softer and more friable by fatty degeneration 
and this diminution of resistive power against mechanical influ- 
ences may have serious consequences, as rupture of a degenerated 
liver or of arteries with degenerated walls from increased blood 
pressure. Advanced grades of fatty degeneration have, as might 
well be expected, a serious influence upon cellular function apart 
from the fact that this process is in itself an indication of patho- 
logical disturbance of the cellular protoplasm. For example, an 
intense fatty degeneration is capable of decidedly diminishing or 
entirely destroying the contractile power of muscular fibres (a cause 
of cardiac dilatation and paralysis of the heart). In exceptional 
circumstances the process may be distinctly favorable to efforts 
to effect recovery, facilitating the resorption or removal of in- 
jurious substances like tumors or foci of purulent softening in the 
tissues. 

Hyaline Degeneration. 

The transformation of a tissue into a microscopically homo- 
geneous, glassy or transparent, colorless and highly refractile 
coagulum is known as hyaline degeneration. There are produced 
as a result of this change one or more types of albuminates, sepa- 
rable chemically from each other with difficulty, the substance, 



200 



Retrogressive Processes. 



hyaline (v. Recklinghausen), being characterized by its resistance 
to acids, by being uninfluenced by water, alcohol or ether, and by 
the fact that it is brilliantly stained with acid aniline dyes (eosin, 
orange) and with carmine. 

This degeneration, or, as Diirk calls it, homogenization, occurs 
according to Ribbert as a local metabolic disturbance, in which the 
tissues do not properly use up the proteid supplied to them; do not 
assimilate it all or throw it off before it is completely converted. 
Such substance is then precipitated all through the tissue overlying 
the intercellular substance and destroying the latter and the cells 
themselves (Ribbert). Hyaline formation is met principally in 

connective tissue and the vascular 
apparatus, in hemorrhagic and 
anaemic infarcts, thrombi, false 
membranes, in the areas of casea- 
tion and in the connective tissue 
of tuberculous lymph glands, in 
neoplasms ; and to some extent the 
substance occurs as a secretory 
product, as the hyaline cylinders 
of the uriniferous tubules. 

[A number of pathologists use 
the term hyaline in a broad sense 
to include the entire group of 
changes productive of a homogen- 
eous and more or less glass-like 
substance, as amyloid, colloid and 
mucinous material, as well as that 
above referred to ; inasmuch, how- 
ever, as these are capable of dif- 
ferentiation from the substance in 
hand, it seems well to consider 
them separately. The relation of 
hyaline degeneration to coagula- 
tion necrosis as intimated by the 
above description is clear, the hya- 
line change suggesting from its ap- 
pearances and results the so-called 
fibrinoid product referred to in the discussion of coagulation. Hya- 
line substance is, however, not entirely uniform, and the result of 
further study may be expected to further differentiate it into a num- 




Fig. 29. 

Muscle of horse (hsenioglobinseniia. 
ten days after attack) ; a, nor- 
mal fibre; b. hyaline lumps. 
(After Zsehokke.) 



Hyaline Degeneration. 201 

ber of similar but not identical albuminates. There are minor dif- 
ferences recognized among the different examples in the ' staining 
reactions, which indicate this multiplicity, but as yet it is impossible 
to indicate a clear basis of separation. As a result of this uncer- 
tainty, however, there have arisen a number of types tentatively 
spoken of as forms of hyaline degeneration. Thus, the hyaline met 
in dense connective tissues as scars, walls of sclerotic blood vessels, 
etc., is usually regarded as the typical form, the fibrous tissue here 
forming minute or grossly visible masses of the glassy transparent 
matter, and grossly presenting an appearance very similar to hya- 
line cartilage, the material being of about the same consistency 
as the latter. Another form is met in tuberculous and syphilitic 
lesions as a precursor of the later caseous change ; it is spoken of 
as a "necrotic hyaline" and is apt to exist only in microscopically 
appreciable amounts, but under the microscope presents the same 
general appearances as the typical variety. In muscle a hyaline 
change minutely distinguishable by the uniform alteration of the 
muscle fibre into a homogeneous, glassy, cylindroid area or by the 
formation of lumps of such a material within the fibre, and occa- 
sionally extensive enough to give the tissue, when grossly examined, 
a peculiar boiled appearance, is met in typhoid fever (Zenker's 
hyaline degeneration) in man, in the hsemoglobinaemia of horses, 
and in a variety of infectious diseases and local inflammatory 
changes in muscle in various forms of animal life. This variety 
closely resembles coagulation necrosis. In the blood a variety of 
hyaline thrombi, usually minute and representing the primary forma- 
tion of the clot, is due to a fusion of blood plaques or of blood 
plaques and leucocytes ; and in old clots a change often spoken of 
as "blood hyaline," leading to more or less homogenization of the 
cellular and fibrinous constituents of the clot into a transparent, 
structureless and yellow-colored (microscopically) or reddish 
(grossly) material. Definite fibrinous exudates, as that of pleurisy 
or pericarditis, and that of false membranes, as of diphtheria, 
sometimes undergo a similar change (exudative hyaline), losing 
all the reticular appearance of the earlier stages and presenting 
uniformly glass-like sheets or bands or clumps of hyaline matter. 
Within tumors, especially sarcomata, hyaline matter is often found ; 
in some of the sarcomata mantles of the substance form over the 
blood vessels or actually involve the vessels and render them im- 
pervious (cylindromata). In various changes and in various situa- 
tions in the body, rounded, spheroidal, minute masses, often show- 



202 Retrogressive Processes. 

a concentric marking in section, and reminding one of the well- 
known corpora amylacea, but not responding to amyloid reagents, 
are occasionally met, especially along the blood vessels; these have 
the appearance of hyaline matter and are tentatively classed with 
this type of degeneration. Within the cells as well as between 
them, in a number of tumors small globular masses responding to 
the acid aniline dyes and having a hyaline appearance are not in- 
frequently seen (Russel's acid fuchsin bodies) ; they were, when 
first noted, interpreted by some as of parasitic nature, but are now 
looked upon as a degenerated substance. The same bodies are not 
very uncommon within the various cells, as those of the liver or 
kidneys, in animals not subjects of neoplasms (intracellular 
hyaline). 

From the fact that these and even other examples are all re- 
ferred to this process the confusion in our prevailing ideas must 
be evident. The term "hyaloid" is often employed in order to 
evade somewhat this confusion, when it is sought to describe a 
clear, uniform, structureless substance suggesting true hyaline, 
but not giving perfect staining reactions and not corresponding 
chemically with amyloid, mucinous or colloid matter. 

The cause of the change in a broad sense includes disturbances 
of nutrition and the influence of local intoxications, but the details 
of the action of these and of the development of hyaline and hya- 
loid substances are confused and largely wanting. The change is 
probably often that of a true coagulation necrosis ; in some forms 
it involves further alterations of coagulated matter; in others it 
evidently does not mean the necrosis of the cells involved, but by its 
advance leads to their death, and is thus rather a true metamorpho- 
sis. When tissues are the seat of this change in its complete devel- 
opment they are entirely functionless and dead ; and the hyaline 
material after a variable time becomes the seat of fatty degeneration, 
usually advancing to caseation and either softening or becoming 
the set of terminal calcification. There is no evidence that indi- 
vidual cells containing small globules of hyaline substance are 
seriously incommoded by it, although the part of the cellular pro- 
toplasm thus affected is probably useless and if the cells be greatly 
involved it is probably eventually a serious lesion.] 

Mucoid Degeneration. 

The mucus or mucin which is secreted by the mucous glands 
of mucous membranes and is normally found in tendon sheaths, 



Mucoid Degeneration. 203 

bursae, synovial membranes and in notable quantities in foetal con- 
nective tissues, is often produced in excessive amounts in pathologi- 
cal conditions and found in such quantities in the matrix of tissues 
that it becomes evidence of a degenerative process. Increased se- 
cretion of mucus from cells occurs for the most part as one of 
the phenomena of inflammatory irritation, the mucus appearing as 
an accumulation of a ropy fluid, resembling the albumen of an 
egg (mucous catarrh), sometimes more or less clouded from the 
admixture of desquamated and exuded cells. In connective tissue, 
cartilage and bone, the occurrence of mucus causes a gelatinous 
swelling, an appearance suggestive of head cheese. 

Under the microscope mucus may be recognized as transparent 
droplets coalescing into clumps (mucous spheroids), usually having 
fairly definite outlines. The cells in which the mucus is formed 
generally swell up in one part, the mucin causing some nuclear 
deformation from pressure, flattening it and pushing it toward 
the base of the cell (transformation of cylindrical cells into goblet 
cells) ; the mucus seems to originate from the nucleus in the form of 
a chromatic substance thrown off in small globules (hyalosomes), 
which take a uniform blue color with hematoxylin and respond 
to the xanthroproteic test (yellow coloration with nitric acid). 

[Mucoid connective tissues, under the microscope, are typified 
by the gelatinous structure of the umbilical cord, and present a 
delicate network of stellate cells, with mucin existing within the 
reticular spaces as a transparent structureless intercellular sub- 
stance.] 

Physically, mucin is characterized by swelling in water and the diffi- 
culty of passing it through a filter ; chemically it is precipitated in white 
flocculi by the addition of acetic acid (mucoid softening), but is not 
precipitated by ferric chloride, mercuric chloride and nitrate of silver. It 
is insoluble in alcohol and ether. There are apparently a number of 
forms of mucin (Birch-Hirschfeld), among them some which are not 
thrown down by acetic acid (pseudo-mucin, metalbumin). [Three types 
are commonly recognized, mucin, pseudo-mucin and paratnucin. The first 
and second are usually found as products of epithelial cells ; the third 
is more apt to be met in mucoid degeneration of connective tissue. Mucin 
and pseudo-mucin when heated with a mineral acid give origin to a 
substance capable of reducing Fehling's solution; paramucin will reduce 
it directly. They all, as a rule, take a blue stain with ha?matoxylin, but 
vary in their staining properties with aniline dyes. It should be noted 
here that the mucoid cells, really "goblet epithelium," of certain cancers 
were formerly regarded as colloid, and at present are often thus spoken of ; 
but it should be definitely understood that these so-called colloid cancers 
are improperly named, and should be denominated mucoid cancers.] 



204 Retrogressive Processes. 

Mucoid degeneration of tissues should be considered as a de- 
structive change ; but the increased secretion of mucus may have 
a favorable influence in pathological conditions, by the envelopment 
of harmful corpuscular agencies and thus preventing inflammatory 
irritation (dust particles, bacteria from the bronchial tubes, larynx, 
pharynx and nose). 

Colloid Degeneration. 

Under the term colloid substances are included a number of 
products of a gelatinous, brownish and tenacious character, remind- 
ing one of half-set carpenter's glue, which, like mucus, originate 
from the cells in droplets, appear under the microscope as hyaline 
balls and clumps and are entirely insoluble in alcohol, ether and 
both hot and cold water. The substance differs from mucus, how- 
ever, in being completely soluble in acetic acid after a preliminary 
swelling. This substance is normally found in the thyroid and 
prostatic glands. Hypersecretion of the material leads to the forma- 
tion of cysts (goitre of the thyroid gland, adrenal cysts in the 
horse), which occasionally attain considerable dimensions (size of 
a fist). [The cause of the process is unknown, but there is reason 
to suspect that the product is the result of a change which follows 
the fusion of the blood coloring matter with some of the mucins. 
It involves epithelial structures, commonly the thyroid, but is not 
infrequently met in the kidneys, adrenals, ovaries, the cerebral hy- 
pophysis and elsewhere in the body. The colloid material is com- 
monly found collected in spaces lined with epithelium (or spaces 
which probably were originally so lined), as cysts which range from 
a minute size to that of a walnut or rarely even that of a fist. The 
substance is an albuminate of uncertain and probably variable com- 
position. Its stiff gelatinous consistency, brownish-yellow color 
and transparency, together with the other features above mentioned, 
grossly differentiate it from mucus and the hyaline substance. 
Microscopically the material is of a transparent, structureless ap- 
pearance with yellowish tint, and typically takes the acid stains. 
Y\ nen within the cells and before merging with the general colloid 
mass, the substance is colorless and appears in globules and small 
clumps, which, however, eventually fuse homogeneously with the 
mass of colloid in the acinus or cell-lined space. The cells thus 
affected are apparently not altered primarily and are affected mainly 
by the pressure of the collection of the colloid matter, which causes 
more or less atrophy.] 



Gly 



ico genie Infiltration ; Amyloid Change. 



20: 



Glycogenic Infiltration. 

The glycogen which is physiologically stored up in the liver 
and which is also met in muscle, kidneys, uterus, placenta, cartilage, 
squamous epithelium and in all of the organs of the foetus, may, 
when circulating in abnormal amount in the blood (diabetes mel- 
litus) be found in still other cells, being present in considerable 
proportions in such circumstances in the leucocytes and renal 
epithelial cells. It is also found in pus corpuscles in suppurative 
affections, and in tumors of embryonic derivation the cells con- 
tain glycogen. This con- 
dition can scarcely be re- 
garded as a special degenera- 
tion, as the glycogen-bearing 
cells show no other features 
of alteration. The glycogen 
exists in the cells merely 
in the form of globules of 
larger or smaller size, clumps 
or granules, staining brown 
with iodine and readily solu- 
ble in water (or saliva). 

[The condition known as 
wdophilia, met typically in 
septic conditions, is due to 
the presence in the leuco- 
cytes of these iodine staining 
granules of glycogen. This 
condition is demonstrable bv 
making films of blood from such cases ; these, while still moist, 
being allowed to dry over iodine crystals.] 

The condition is probably only an unusual metabolism, an ex- 
ceptionally rich glycogen infiltration, in which, possibly, as sug- 
gested by Ehrlich, the glycogen was uniformly distributed in the 
living cells and separated in drops and lumps only as a post- 
mortem phenomenon. 




Fig. 30. 

Glycogenic infiltration of the liver cells ; 
X 1,000. (After Thoma.) 



Amyloid Degeneration. 

The name amyloid (amyliim, starch; eUos , nature of) was ap- 
plied by Virchow to a substance which gives a color reaction 
when treated with iodine and sulphuric acid somewhal similar 



2o6 Retrogressive Processes 



s 



to that of starch [when treated with iodine alone], and which is 
found in the tissues as the result of a special process of meta- 
morphosis. 

[The editor is accustomed to regard the process not as a 
metamorphosis or true degeneration as here indicated, but rather 
as an infiltrative process. The reasons for this view are, it is 
true, not absolutely convincing, but are suggestive. The material 
may in accordance with this idea be supposed to exist in the 
blood or elsewhere in a soluble pre-amyloid state and to be car- 
ried by the blood to be deposited in its favorite seat, the walls 
of arteries, where for some unknown local cause it is precipitated 
as amyloid matter. Its common occurrence in the walls of arte- 
ries rather than those of veins, its appearance in masses in inter- 
cellular positions where normally there scarcely exists material 
which could by any known mode of transformation assume the 
size of the common amyloid masses (as between the basement 
membrane and epithelium of the renal tubules), are the principal 
basis for this opinion.] 

When unstained, amyloid substance is, like hyaline or colloid, 
of a glass-like, homogeneous appearance, and is principally found 
deposited in the connective tissue framework of the blood vessels 
in affected organs as lumpy, swollen-looking, trabecular or clump- 
like masses. While, however, the hyaline above discussed is 
tinged like the tissues themselves a yellow straw color by iodine ; 
amyloid substance takes a mahogany-brown tint, sometimes with 
a violet tone, and stands out conspicuously from the tissue. If 
dilute sulphuric acid or zinc chloride be applied to such a prep- 
aration, the amyloid substance takes on a deep violet to black 
color; its reaction being thus somewhat similar to that of starch 
granules or cellulose, these, however, becoming blue directly on 
the application of iodine alone. Other color reactions, charac- 
teristic of amyloid substance, are given by various aniline dyes ; 
methyl-violet staining it a ruby red, methyl-green a reddish 
violet, in contrast to the bluish violet or green color given the 
normal tissues. Amyloid is colored yellow by nitric acid, indi- 
cating by this xanthoproteic reaction its albuminous nature. 

According to the investigations of Krawkow this substance is 
a compound of an albuminate with chondritin-sulphuric acid. 
This latter substance, to which the iodine reaction is mainly due 
(Ribbert) is found normally in cartilage and elastic tissue. 
Amyloid material, as such, does not exist normally in any part 



Amyloid Infiltration. 207 

of the body, but results from some disturbance of metabolism. It 
woud appear that a hyaline, which either does not respond to 
the above reactions at all or only partially, is a precursor of 
amyloid. 

Amyloid degeneration occurs especially after protracted sup- 
purations ; this, and the fact that its deposition mainly takes place 
in the connective tissue structures of blood vessels make it 
plausible that some unused albuminate passes from the local sup- 
purative areas into the blood and is deposited by the latter in 
the tissues, where by the combination with the chondritin-sulphuric 
acid it is changed into amyloid matter (Ribbert). Experimental 
production of amyloid change lends some weight to this idea ; 
abscesses have been produced in animals by injection with 
pyogenic bacteria and predisposing chemicals (oil of turpen- 
tine), and amyloid matter found in various organs after the 
abscesses have existed for a long time (Ribbert). However, not 
every suppurative process results in amyloid change ; special 
nutritive disturbances are also required for its production. 

' The process is far more commonly seen in man than in 
animals. In man it is an ordinary accompaniment of advanced 
tuberculosis, aside from its occurrence in chronic suppurations ; 
but it is usually absent in this connection in animals, although it 
has been observed as a degenerative accompaniment of tuber- 
culosis in birds (Leisering, Roll, personal observations). In 
horses it has been encountered a number of times, especially in 
the liver by Rabe. 

Organs, the seat of amyloid infiltration, become considerably 
enlarged ; their consistence is changed, becoming dense and 
inelastic and more or less wax-like ; in section the tissue is 
somewhat transparent and homogeneous, and is pale from an 
anaemia. In man amyloid livers are suggestive of such names as 
bacon-like livers, waxy livers or zuooden livers; in the domestic 
animals amyloid livers have a somewhat different consistence, 
the decidedly enlarged organ (in the horse reaching eight to 
fourteen kilograms in weight) becoming friable, and therefore 
having a tendency to rupture. In the spleen, both in man and 
animals (hog, dog), the process occurs either as a diffuse firm 
enlargement of the organs with a translucent red or grayish red, 
homogeneous appearance of the whole substance suggesting an' 
analogy to smoked salmon or bacon (ham spleen, bacon spleen), 
or as a change limited to the splenic follicles, which in this case 



2o8 Retrogressive Processes 



& 



stand out like swollen sago-grains (sago-spleen). In the kidney 
the substance is likely to be deposited in the glomeruli, giving in 
these early cases the appearance of glassy granules ; in more ad- 
vanced cases the whole organ may, however, become waxy and firm. 
Microscopic study shows very clearly in these structures the 
deposition just outside the capillaries and along the connective 
tissue elements of the larger blood vessels. In the advanced 
stages of the process the substance is seen in thick homogeneous, 
bulging and lumpy strands. The glandular cells and connective 
tissue corpuscles generally only suffer passively by pressure 
atrophy, that is, they do not themselves become amyloid ; Johne, 
however, states that in the horse the liver cells also become en- 
larged, lobular and shining and lose their nuclei, this indicating, 
therefore, their participation in the process. 

Amyloid infiltration may also occur as a purely local process, 
especially in the connective tissue of tumors and inflammatory 
thickenings of mucous membranes having a substructure rich 
in elastic tissue, as in the growths in the nasal mucous mem- 
branes of horses known as narioblastomata. 

Finally, amyloid may be met in the form of concrement-like 
deposits. The hyaline casts [waxy casts] forming in the urinary 
tubules in inflammations of the kidneys sometimes show amyloid 
reactions ; so, too, the round granules made up of epithelial 
conglomerations and showing a concentric structure, which 
are found in the prostate in man and in old dogs and oc- 
casionally in the ependyma of the cerebral ventricles (Bruck- 
miiller, Johne). These bodies are known as corpora amylacea or 
versicolorata in case they are colored brown, red and violet by 
tincture of iodine and sulphuric acid ; and as corpora Hava when 
they are merely turned yellow with iodine. Because of the 
lack of uniformity of these color reactions, and because amyloid 
substance in its earlier phases exhibits only the general charac- 
teristics of hyaline, it is reasonable to suppose that albumens, so 
modified as to appear hyaline, are precedents of the amyloid 
material. 

The pathological significance of amyloid degeneration depends 
upon the extent to which it has proceeded. Small local deposits 
are merely incidental. In diffuse infiltration the progressive 
character of the process, the marked increase of the volume 
of the organ, the consequences of pressure atrophy on the paren- 
chymatous cells, constitute the most important factors in pro- 
duction of immediate funtional disturbance of the organ. 



Pigmentation. 209 

Pigmentation. 

Autochthonus Melanosis. — Normally the epithelial cells of 
the cuticle, especially the deeper layers of the rete Malpighii, the 
hairs and horns, the epithelium of various ingrowths from the 
skin (for example, the mouth in dogs), besides the pigmented 
epithelium of the retina and many ganglion cells, and in a num- 
ber of situations the connective tissue elements (the cells of the 
choroid, sclera, pia, and also the cutis), contain in variable 
amounts coloring substance in the form of yellow, brown or 
black granules (the former hoemofuscin; the latter, melanin). 

The origin and formation of this pigment are as yet not en- 
tirely clear. The entire lack of similarity to blood pigment, 
especially the absence of iron as a constituent, the pigment granules 
being, however, rich in sulphur and containing nitrogen 
(v. Nenski, Sieber, Abel, Davids and Schmiedeberg) , would in- 
dicate that these granules are transformed from the albuminates 
formed within the cells as products of a peculiar ("metabolic/' 
from /xerapdWeiv , to transform, to change) cellular activity. It is 
not known whether the material employed in the pigment pro- 
duction is originally derived from the blood or whether it repre- 
sents an excretory substance of the system and its production is 
comparable to the formation of humus ; it can only be said that 
in the same way as in early fcetal life and thence onward, forma- 
tion of blood coloring matter takes place from the influence of 
cellular activity, or as, under the influence of light, chlorophyl 
formation is a form of cellular function, these pigments are de- 
veloped within the cells. 

Connective tissue cells have been noted in the human coriuni loaded 
with pigment and capable of movements which actually carry the pigment 
into the epithelial cells, and in some circumstances carry it away again 
(chromatophores) . This has been observed particularly in connection with 
experimental transplantations; where a small bit of white skin has been 
grafted upon a black (negro), after healing it becomes as dark as the 
neighboring tissue from the penetration of chromatophores. and vice versa 
in transplanting black skin upon a white person, loss of color takes place 
in the graft by convection of the pigment through * the agency of the 
wandering chromatophore cells to the lymph glands. (The existence of 
these wandering cells has been doubted by Kromaycr.) According to 
C. Gessard, the black pigment, especially of melanotic tumors, is produced 
from oxidation of tyrosin (by an oxygenating diastase called tyrosinase') 

An increased accumulation of" autochthonous pigment, a hyper- 
pigmentosis or hyperchromaiosis, occurs in the human skin in the 



210 Retrogressive Processes. 

form of brown or black patches, as similarly colored papillary 
hypertrophies in the pigmented moles (naevi), freckles (ephelides), 
liver spots (chloasmata), lentigo; and is also met in increased 
pigmentation of the cardiac muscle, of the enteric musculature 
and in a special type of cutaneous pigmentation occurring in a 
general disease (Morbus Addisonii). In some of the domestic 
animals the congenital, brown, lentiginosis spots are, according 
to Schindelka, quite common ; the condition known as melanosis 
maculosa in calves is especially frequent, such an excess of pig- 
ment cells existing congenitally that spots of inky blackness may 
be found in large numbers beneath the skin, between the muscles, 
beneath the pleura and in the lungs, in the epicardium, in the 
liver, in the submucosa of various mucous membranes and in the 
membranes of the central nervous system. In foci of local over- 
production there may often be observed in sheep an excess of 
the black pigment in the pia mater. There is also seen in calves 
and in adult cattle rather frequently a sepia-brown to ebony 
black color of the kidneys, which, from the studies of L. Roth, 
may be considered due to an infiltration of the epithelium of 
the convoluted tubules and Henle's loops (the thicker limb) with 
pigment granules which, in some cases, were identified as melanin, 
in others as biliverdin. Unquestionably the pigment of melanomata 
or melanosarcomata (cf. Tumors) is produced by metabolic ac- 
tivity; the proliferating cells contain within the protoplasm brown 
and black granules in thickest profusion. According to the in- 
vestigations of Berdez and Nenski the coloring matter of the 
melanotic tumors is rich in sulphur; it is known as hippomelanin 
and phymatorhasin. 

Haematogenous Pigmentation, Hcumochromatosis^ — The color- 
ing matter of the blood, haemoglobin, in all conditions causing 
haemolysis or destruction and washing out of red blood cor- 
puscles, becomes freed from the cells ; and is partly distributed 
in solution throughout the fluids and tissues, and may be in part 
precipitated, as is indicated by the pigmentation of the tissues. 
In the event of large numbers of red corpuscles undergoing 
solution (haemolysis) within the blood passages, as in various 
intoxications and infections (blood poisons, piroplasmosis), the 
coloring matter (haemoglobin or methaemoglobin) is transferred 
to the blood plasma. The blood becomes lake-tinged, and the 
serum obtained after venesection from the clot is stained, instead 
of limpid and yellowish, a deep red (hcemoglobincemia) . The 



Pigmentation. 



211 



dissolved coloring matter may pass into the urine, producing 
hemoglobinuria and met hemoglobinuria in which conditions the 
urine assumes a bloody, dark-red or brownish black appearance. 
Precisely as in normal life, the dead blood cells and their remnants 
are taken up by leucocytes and carried to the lymph nodes, spleen, 
bone marrow and elsewhere ; in cases of exaggerated destruction 
of the erythrocytes the same methods of transportation are car- 
ried on in greater measure, and the remnants of haemoglobin are 
deposited in the various organs in proportion as this blood refuse 
fails of complete destruction. Some of these derivatives retain 
their iron (hemosiderin) , as shown by microchemical reactions 
(blackened by ammonium sulphide ; bluish green color on addition 
of yellow ferrocyanide of potassium) ; others contain no iron 
(hoemofuscin and bilirubin) and may be seen as yellowish or brown 
granules and clumps or as a diffuse, rust-colored or yellowish im- 
pregnation of the tissues. 




Fig. 31. 

Haemoglobin crystals from the blood of a 
dog killed by chloroform inhalation ; 
X 230. (After Thoma.) 



Fig. 32. 

Haematoidin crystals from a 
large centrally softened 
blood extravasation in the 
peritonea] cavity ; X 250. 
i After Thoma.) 



Hemorrhagic foci give rise to very profuse hematogenous pig- 
mentation, both the minute extravasations arising by diapedesis 
and the larger haemorrhages ; depending upon the amount of color- 
ing matter deposited and the age of the lesion they cause a 
rusty, ochre-like to black or slate-colored discoloration of the 
tissues. The haemoglobin at first diffuses from the escaped blood 
corpuscles and soaks through (is imbibed by) the tissues in the 
neighborhood of the haemorrhagic focus; the washed out cor 



212 Retrogressive Processes. 

puscles disintegrate and are carried off by other cells, especially 
leucocytes, by their phagocytic action. Just as in the above-men- 
tioned intravascular liquefaction of the blood cells, the haemoglobin 
in its freed condition is changed into amorphous masses and 
granules of a yellow or reddish-brown color, partly deposited in 
the intercellular substance of the tissue and partly taken up by 
leucocytes, endothelial and other cells. Blood extravasations may 
also contain crystalline deposits especially in the form of rhombic 
plates and needles of a ruby-red or yelowish-red tint, known as 
liccmatoidin (identical with bilirubin). This is particularly seen 
where fluid blood remains stagnant for a long time. 

Tissues discolored by hemosiderin may become slate-colored or black- 
ened (formation of iron sulphide, pseudomelanosis) in places where they 
come in contact with sulphuretted hydrogen (in the intestinal canal after 
death, or in ichorous cavities and putrefying hemorrhagic exudates). 

Icterus, Jaundice. — Staining of the tissues by biliary coloring 
matter is known as icterus (6 iKrepos) ; it occurs as the result of 
the entrance of bile or biliary pigment into the blood und 
fluids of the body. The common causes of such absorption of 
bile are diseases which occasion obstruction to its passage to the 
intestine, and therefore result in a biliary stasis {icterus from 
stasis), and all conditions which are accompanied by obstruction 
or narrowing of the biliary channels (obstruction from gall stones, 
compression by tumors, swelling of the mucous lining of the 
passages), providing the liver tissue meanwhile continues its pro- 
duction of bile. (In hepatic diseases which lead to destruction 
of the liver cells or to a lowered production of bile, of course 
obstruction of the ducts cannot occasion any jaundice or only 
minor grades of the symptom, as may be observed in distomiasis 
of the liver, in which condition this feature is usually absent.) 
In case the bile can no longer escape it first collects in the bile 
capillaries. This may be observed under the microscope as an 
engorgement of the intraacinous biliary tubes which look as if 
actually injected with greenish bile substance ; and the stasis may 
be further traced into the intercellular secretory alveoli and 
tubules. In case of rupture of these delicate capillaries the bile 
may gain entrance into the adjoining lymph-spaces, and be car- 
ried by way of the lymph channels into the blood (thoracic duct). 

At other times it probably escapes directly from the liver cells into 
the blood capillaries; it is assumed that within the liver cells, in addition 
to the biliary secretary vacuoles, there is another canalicular system which 
carries urea and sugar into the blood capillaries. (Nauwerk, Browicz.) 



Pigmentation. 213 

Biliary stasis may also depend upon an excessive production 
of the secretion, inasmuch as the profusely produced bile may 
also be sometimes too concentrated and thick and flow with 
difficulty, the cells in consequence becoming clogged. A hyper- 
cholia of this type occurs in conditions which cause a marked 
destruction of red blood cells, and the haemoglobin set free 
en masse is then worked over in the liver and renders the bile 
particularly rich in its pigmentary matter. It is possible, too, 
that the bile may be thickened and less fluid or may diffuse 
directly into the blood vessels because of disease of the liver cells. 
This is met in a number of intoxications and infectious diseases, 
where, as the cause of the jaundice cannot be referred to a condi- 
tion of biliary stasis, it is spoken of as a resorption jaundice or 
infections or toxic paracholia. (Pick.) 

It was formerly believed that the formation of biliary coloring matter 
in quantities sufficient to cause jaundice could also take place outside 
the liver, in the blood; and a hsematogenous jaundice was spoken of. 
From the studies of Minkowski and Naunyn, however, it may be consid- 
ered established that, even in cases where a simple increase of destruction 
of erythrocytes causes this symptom, it is not produced except with the 
intervention of the liver, and that the transformation of the haemoglobin 
into biliary pigment is accomplished in the liver. Birds jaundiced by 
arseniuretted hydrogen rapidly lost their icterus after extirpation of the 
liver, and where the liver had been previously ablated, jaundice could not 
be produced in any degree at all. [The term "local hematogenous jaun- 
dice" is sometimes applied to the yellowish discolorations of fading bruise 
marks; it is permissible only in a general way, and in precise discus- 
sions the pigment must be understood as not identical with the jaundice 
pigment. Although there may be more or less hsematoidin present, there 
are also less closely allied blood pigments.] 

The entrance of the bile into the blood is followed by an 
impregnation of all the tissues to which the blood vessels are 
distributed with the biliary coloring matter, this giving them a 
biliary tint of various shades. In the living body this is apt to 
be particularly conspicuous in the conjunctiva and sclera; in the 
dead animal the yellow color is principally apparent in the sub- 
cutaneous tissues, the fat, intermuscular connective tissue, the 
lungs, liver and kidneys, the mucous membranes and their mus- 
cular coats. Where the normal color of an organ was pale the 
discoloration may take on an intense citron-yellow hue ; the dark 
liver and kidney tissue becomes saffron yellow to olive green or 
greenish-black. Even the bones as well as fibrinous blood clots 
and the blood serum assume a biliary tint. As the pigment gains 



214 Retrogressive Processes. 

access to all the glands their secretions also become yellowish ; 
and the pigment is especially noticeable in the urine. [The 
saliva, gastric and pancreatic juice, tears and mucus are apt 
to be free from coloration.] Only cartilage, the cornea and 
the enamel of the teeth, and, too, the brain, take up but little of 
the color. Because of the diffuse uniformity of impregnation 
of the intercellular substance and of the cells with the coloring 
matter, it at times is not noticeable under the microscope (per- 
haps washed away in the details of preparation of the specimen) ; 
but in other instances some of the cells, as those of the liver, are 
stained an intense yellow or yellowish-brown, and granular and 
coarser deposits of a yellow, brownish or green color are found 
in the protoplasm, especially in the hepatic and renal epithelial 
cells. The pigment is sometimes seen in crystalline form (ruby- 
red rhombic plates of bilirubin) in the kidneys, spleen and bone 
marrow. 

Jaundice may be a transitory condition ; the liver after removal 
of the interference to the passage of the bile resuming its 
normal functions and the resorbed bile being eliminated by the 
urine, etc. In case of more prolonged duration faults of the 
organism become apparent. In the first place the absence of a 
sufficient amount of bile in the intestine may interfere with diges- 
tion; in the second place the bile stasis in the liver may cause 
pressure upon the liver cells and can give rise to degenerative 
and necrotic * changes ; thirdly the mingling of the bile with the 
blood brings into the latter and into the different organs sub- 
stances which are hemolytic and have other toxic influences. 
The biliary coloring matter and, too, the biliary acids are to be 
included among such toxic substances, the latter undoubtedly being 
toxic to the nervous system. [It is supposed that the itching 
complained of by jaundiced human beings, and to some extent 
present in animals, is due to an irritation of the skin by the 
biliary pigment; and the slowing of the cardiac rate in jaundice 
is directly referable to the action of the biliary acids or their salts 
upon the vagus, or in marked instances upon the heart itself.] 
Moreover, the influence of substances produced in intestinal putre- 
faction should be kept in mind, these materials being absorbed 
from the intestines and passed through the diseased liver which 
is no longer able to neutralize their poisonous properties. Severe 
cerebral symptoms developing in cases of biliary obstruction and 
sometimes fatal (convulsions, coma, delirium), accompanied by 



Pigmentation. 215 

high fever, indicate the existence of such an autointoxication, 
which is designated as icterus gravis and cholcemia. 

Exogenous Pigmentation. — When the tissues are impregnated 
with pigmentary substances which gain access to the body from 
the exterior the process is known as exogenous pigmentation. 
The most common example is the deposition of carbonaceous ma- 
terial (anthracosis) in the lung, practically always found in man 
from inhalation of the particles ; it also occurs in dogs which 
are compelled to pass much of their time in smoky places, 
and in horses kept for a long time in coal mines. The in- 
haled dust, except that which is removed by the bronchial 
mucus and by the ciliary activity of the tracheal cells, re- 
mains suspended in the alveoli [and smaller tubes], is taken up 
by wandering cells (dust cells) ; part being carried in 
the pulmonary lymph channels and reaching the lymph glands 
of the lungs and bronchial tree, part being deposited in the lymph 
spaces of the lungs. Varying with the quantity of carbon thus 
deposited, the lungs and lymph glands become mottled and of a 
gray slaty appearance or uniformly and completely blackened.* 

Dark pigmentations may also be caused by the deposition of 
mercury, lead and silver, observed sometimes after medicinal 
administration of preparations of these metals, as in case of the 
black color of the intestinal villi in the horse after the adminis- 
tration of calomel. It is usually the result of the formation of 
mercuric and plumbic sulphides from contact with the sulphuretted 
hydrogen of the gastro-intestinal contents. In employing nitrate 
of silver in internal medication it is absorbed from the alimentary 
tract and deposited in extremely fine granules (reduced to metallic 
silver) in all the different organs, skin, conjunctiva, kidneys, etc., 
and gives them a grayish pigmentation. The condition is known 
as argyria. 

By means of subcutaneous and intravenous injections of staining 
solutions (carmine, indigo-carmine, methylene blue) the tissues of the body 
may be colored blue or red. The protoplasm of many cells takes up the 
stain diffusely in part ; sometimes instead a granular deposition takes place 
from combination of the pigment with certain granular constituents of the 
cells (Arnold, Ribbert). 

[The effect of external or exogenous pigmentation is usually 
trivial aside from the mere discoloration and is only important 
when intense or as a predisposing cause to more serious dis- 

*For details cf. I'atfi. Anatomie <i. Hauatiere, [I. Anil. Stuttgart, Ferd. EDnke. 



2i6 Retrogressive Processes. 

turbances. Each pigment particle is essentially a foreign body 
and induces a certain amount of inflammatory reaction, usually of 
low grade and productive of an increased amount of fibrous tis- 
sue. Parts the seat of marked pigmentation, as the lungs and 
bronchial glands, become more or less indurated. The possibility 
of infection by tuberculosis, especially noted in man, becomes more 
easy when previous dust inhalation has induced a chronic bron- 
chitis and has induced the secondary faults of pulmonary blood 
and lymph drainage and has lowered the general vital resistance of 
their tissue by a prolonged chronic interstitial inflammation. In 
less important organs than the lungs, of course, the changes occa- 
sioned by external pigmentary deposit are proportionately less 
serious.] 

Calcification and the Formation of Calculi. 

Calcium salts are normally present in solution in the body 
fluids (calcium glycerin-phosphate, carbonate, lactate, oxalate, etc.). 
Deposition of lime in solid form takes place normally in the bones 
and teeth of man and the animals ; and in herbivora there is nor- 
mally excreted in the urine such large amounts of calcium salts 
that by mere cooling they precipitate and the urine at time of 
voidance may even be turbid from their presence (horse). Cal- 
cium impregnates the matrix of bone and teeth with so much 
uniformity of distribution that it is not apparent in definite masses, 
being recognized only by the solidity of the structure and by 
chemical analysis ; in the urine it separates as amorphous granular 
and crystalline forms. 

The deposition of calcium salts in other parts than those men- 
tioned is pathological and is known under the names calcification, 
cretaceous infiltration, petrification and incrustation. 

The basis for this deposition is probably to be sought in the 
removal of the substances favoring the maintenance of the lime in 
solution, as free carbonic acid, and the transformation of earthy 
salts, which are soluble in water, into insoluble calcium compounds, 
and, too, in increased supply of lime. Thus, pathologically, calcifica- 
tion is apt to occur in dead or altered tissues in which free carbonic 
acid exists in lowered amount and in which gaseous interchange 
by the cells is essentially impaired, or may appear in secretions and 
excretions where it leads to the formation of concretions. [Klotz 
{Jour, of Exper. Med., 1905, vii, p. 633) has recently attempted 
to explain pathological calcification in necrotic degenerative areas 



Calcification. 217 

upon the assumption of a previous fatty degeneration of these 
structures, soaps of lime being formed primarily by combination 
of lime brought in solution by the juices permeating the altered 
tissues with the fatty acids. These soaps are later further changed 
by substitution -of the fatty acids by carbonic acid and phosphoric 
acid. Wells (Jour, of Med. Research, 1906, N. S. ix, p. 491) can- 
not find evidence of constant and important occurrence of these 
soaps as a stage in the process, although in traces he finds such 
soaps to exist in areas of calcification. Fischler and Gross (Zieg- 
ler's Beitrage, 1905, Festschrift fur Arnold, p. 326) have also 
found evidence of the presence of such soaps in atheroma and in 
the margins of infarcts, but not in caseous areas, and are unable 
to definitely declare that soap formation is an essential stage in 
calcification. Wells regards pathological calcification as probably 
essentially similar to normal deposition, and inclines to the idea 
that there exists or is produced in the area some substance having 
particular affinity for calcium, although he is unable to indicate its 
nature ; it is not, however, dependent upon the vital state, as in 
cartilage it exists both when the cartilage is living and after 
it is boiled.] 

In distinction from physological calcification, in which a perfectly 
homogeneous combination of the lime with the matrix obtains, patholog- 
ical calcification is manifested on microscopic examination by the presence 
of fine, highly refractile granules, looking like particles of fat and pig- 
ments, which, with direct light (complete closure of the substage dia- 
phragm), have a dull, glistening, whitish appearance, and are found both 
within and between the cells. On the addition of acids (especially hydro- 
chloric acid) the calcium salts are dissolved and the presence of calcium 
carbonate is indicated by the immediate effervescence (carbonic acid). With 
pure sulphuric acid great numbers of crystals of gypsum (calcium sulphate) 
separate in delicate pointed crystals, scattered all through the tissue. A 
calcified tissue (the same in case of partial calcification) takes a very 
intense dark blue stain with hematoxylin. 

Ossified tissue differs from merely calcified structures by the forma- 
tion of lamellae of the matrix (Haversian lamellae) and the inclusion 
of the bone cells in the intricately branched lacunae. 

Petrification of tissues renders them as hard as bone and gives 
them a dirty white appearance. As a senile change this is occasion- 
ally met as spots isolated in the cartilaginous nasal septum in cattle. 
in the laryngeal cartilages of dogs, and quite uniformly in the costal 
cartilages of old animals. (These foci become easily visible as 
opaque points on drying the cartilage.) With much less frequence 
than in man, calcification of the vessel walls is observed in animals 



2l8 



Retrogressive Processes. 



as a rather rare occurrence, transforming the intima of the vessel, 
as the aorta, into a rough, scaly surface, or appearing as flat plaque- 
like or disc-like areas, making the vessel at such places rigid and 
inelastic. The greatest tendency to this change is found in the 
large verminous aneurisms in horses, which form brittle, hard 
enlargements of the arteries. The intima and the media in these 
lesions are the especial seat of the calcification, preceded by hyaline 
degeneration. 




Fig. 33. 

Portion of liver of a horse with calcification of necrotic parasitic foci 

Trolldenier. ) 



(After 



In greater measure newly-formed inflammatory connective tissue 
is rather often affected ; thus the cicatrized castration wound of 
the abdominal wall in hogs may be observed changed into a calcified 
plate as broad as a hand, and the opening into a hernial sac in um- 
bilical hernias in the same animals is sometimes changed into a cal- 
cified ring of connective tissue. Calcareous plates in the connective 
tissue of the cow's udder are sometimes found ; and even the con- 
nective tissue of the lungs is in rare instances (in cattle) trans- 



Calcification. 219 

formed into a branched, rigid and corset-like enclosing structure. 
In the dense membranes of the spinal cord, in dogs, calcareous in- 
filtration gives rise to rigid thickenings which feel like splinters 
of wood. Bursse and tendon sheaths in horses may become ex- 
tensively calcified and ossified. The colloid matter often met in the 
thyroid gland and sometimes involving the connective tissue as well 
as the acini, may occasionally terminate in calcification of the organ 
(stone goitre, struma petrificans/m dogs). The herbivora and also 
hogs are with special frequence subject to calcareous infiltration of 
tuberculous caseated tissues. The yellow, cheesy foci produced 
by coagulation necrosis are frequently full of sandy, gritty particles 
and are very hard. In the end dead parasites and the connective 
tissue capsules which are formed about such foreign bodies in the 
parenchymatous organs, as echinococci and round worms in the 
livers of horses, become so permeated with lime salts that they form 
stony, bone-like or mortar-like, chalky masses. 

In women, dead foetuses long retained in the uterus or peritoneal 
cavity may become so completely calcified as to be of stone-like hardness 
(petrified foetus, lithopcedion) ; in our domestic animals the dead embryos, 
which are often found, usually remain more or less leathery, pliable and 
merely mummified. [In the museum of the Medical Department of the 
University of Pennsylvania there is a thoroughly calcified excellent example 
of a lithopaedion taken, after death, from the uterus of a mare, and pre- 
sented to Dr. James of the above-named institution in 185 1 by Mr. Kearney 
of Gloucester County, New Jersey.] 

Zschokke (Schweiz. Archil). 1902) has described a peculiar crystalline 
deposit observed in the liver of a cow confined to the interstitial spaces 
as white foci, scattered here and there. The abundant precipitate was 
made up of rounded and rhombohedral crystals (about the size of white 
blood corpuscles), the chemical nature of which was not precisely deter- 
mined, although with the iodine-sulphuric acid test they showed some 
relation to cholesterin. 

Solid unorganized bodies which are formed in the secretions and 
cavities of the body are called concretions. They are formed by 
the precipitation of salts which have become insoluble ; their chemi- 
cal composition depending upon the ingredients of the normal se- 
cretions and its existing changes, and therefore not uniform. 
Sometimes they contain organic matter mingled with the saline 
constituents ; or they may be foreign bodies or exudates which have 
become encrusted with salts. The fundamental conditions for the 
formation of these bodies include the following : 

1. Super saturation of the saline solution (Klinuner) and dim- 
inution of the medium of solution. Just as the crystalline salt 



220 



Retrogressive Processes. 



separates from a saturated solution of copper sulphate or from 
Carlsbad-Spruclel water, in the same manner the salts of a secre- 
tion, like the urine, may precipitate, especially should there occur 
a loss of its fluid or of substances which keep the salts in solution. 

2. Retention of secretions or excretions in their storage reser- 
voirs. 

3. Chemical decomposition of the secretion, with the formation 
of insoluble products, as may result from the presence of bacteria 
(ammoniacal fermentation). 

4. Presence of a foreign body or any organic material which 
serves as a nucleus for the deposition of crystals, or as a supporting 

framework for the precipi- 
tated salts, as bits of wood, 
particles of food, or viscid 
degenerative products. 

Urinary Calculi ( Uro- 
lithiasis f gravel, concre- 
menta urinaria). — The sa- 
line constituents of the 
urine may be precipitated 
in the kidneys, in the renal 
pelvis and in the urinary 
bladder and give rise to the 
formation of urinary gravel, 
urinary sand, and larger 
urinary calculi. Even nor- 
mally in the horse, calcium 
carbonate separates in the 
pelves of the kidneys and 
in the bladder from the al- 
kaline urine, the latter being turbid even when freshly passed in 
consequence ; in the other herbivora it becomes cloudy soon after it 
is voided because of loss of the solvent power of its fluid on cool- 
ing. The acid urine of carnivora and omnivora is, on the contrary, 
clear and permits sedimentation only after decomposition and long 
standing. The causes of urinary calculus formation may include 
such structural elements as parasites, blood clots and coagulated 
fibrin, shreds of necrotic tissue, tube casts and epithelial cells, these 
substances affording a place of attachment for deposition of the 
inorganic substances. The presence of living or dead bacteria is 
especially apt to cause precipitation, these at times forming small 




*» 



Fig. 34. 

Urinary calculus from 
horse. 



renal pelvis of 



Concrement Formation. 221 

masses and favoring, as do protein clumps, the adhesion of any 
precipitate, and, too, perhaps causing ammoniacal fermentation. 
A high proportion of salines in the urine is, as pointed out by 
Klimmer, an important feature. This authority questions whether 
the presence of albuminoid or mucoid substances, such as are occa- 
sioned in the urinary tract by inflammation, provides any means of 
cohesion, as a sort of paste. Some such organic stroma is uniformly 
found, especially because the concretions determine a catarrhal pro- 
cess at times, as a result of which layers of mucus and albuminous 
material are found between the mineral deposits ; such viscid matter 
is, however, also found in loose sediments and perhaps may in 
reality interfere with calculus formation by preventing [approxima- 
tion and] cohesion of the particles. Such organic framework is not, 
as pointed out by Moritz, peculiar to calculi, but is, too, an 
important feature in any 
urinary crystal, whatever 
it may be. The size and 
shape of urinary concre- 
tions varies widely with 
the species of animal, the 
site of formation and the 
composition. Renal cal- 
culi are usuallv round, ^^"^ 

J Fig. 35. 

pearl-shaped, like writing Vesical ca]culus from a horse 

sand, millet seed or hemp 

seed ; those of the renal pelvis are irregular, warty, or correspond to 
the shape of the pelvic cavity, crescentic, and may reach a size nearly 
that of a fist. In the bladder the urine throws down a slimy, sandy 
material which forms a thick, soup-like urine or masses which 
may attain several pounds in weight and assume the shape of 
half of a pear (corresponding to the interior of the bladder and 
flattened on one side by the passage of the urine). When com- 
pact, vesical calculi are lentil shaped, oval, flattened or faceted 
from pressure, polished or sometimes rough and mulberry-like, 
gland shaped, and range in size from that of a millet seed to the 
size of a double fist. Small concretions mot with in the ureters or 
urethra, and often impacted in these passages, are not formed in 
this situation, but are swept from the kidneys or bladder. The 
color of urinary calculi is usually brown, metallic, bronze-like : 
some concretions are, however, gray, yellowish or pure white, an<J 
occasionally reddish ones are met. 




222, Retrogressive Processes. 

In construction and chemical composition of urinary calculi a 
large variety of substances take part ; and the concrement is rarely 
made up of but a single chemical constituent, but usually contains 
a number of ingredients. In horses these calculi generally contain 
carbonates and phosphates of lime, carbonate of magnesia, traces 
of iron and occasionally silicates ; those of the cow, sheep and goat 
are at times rich in silicates or magnesium phosphate, but also 
contain calcium carbonate or triple phosphate. In swine they are 
made up either of triple phosphate or calcium and magnesium 
carbonate and phosphate ; and oxylate concretions also occur. The 
uroliths of carnivora are a mixture of calcium carbonate, phosphate 
and urate, or are composed in other cases of uric acid or sodium 






* 



Fig. 36. 
Renal calculi from cow. 



and ammonium urates or of calcium-ammonio-magnesium-phcs- 
phate. The tabular forms, when fresh of soft consistence and of 
greasy, slimy appearance, are mainly made up of cystin. The 
color of urinary concretions is given by the pigment of the urine 
or biliary pigment ; occasionally hsematin has been found to explain 
the existence of a black color, or carbonate of iron that of a 
metallic bronze luster (Fiirstenberg, Pflug, Miiller, Dammann, 
Klimmer) . 

The especial causes of danger in connection with urinary calculi 
are to be found in the disturbances of urinary flow which they 
occasion, giving rise perhaps to urinary retention. In addition 
these foreign bodies act as irritants to the mucous membranes in 



Concrement Formation. 223 

varying grade; may cause dysuria (tenesmus) and pain of intense 
severity (spasm of the involuntary musculature of the ureters, 
bladder and urethra), local inflammation and erosion, obstruction 
of urine, dilatation of the bladder and possibly rupture, hydrone- 
phrosis, and submucous urinary infiltration and urinary intoxica- 
tion of the blood. (For details cf. Spezielle pathol. Anatomie d. 
Haustiere, II. Bd.). 

Gall Stones (Cholelithiasis). — Although in man gall stones are 
comparatively common (25 per cent, of women suffer from them), 
they are rather rare in animals. They are found as soft or half 
solid, slippery bodies in the gall ducts and gall bladder, about the 
size of a hazelnut but sometimes even larger than a fist, usually 
multiple in numbers and often occurring in hundreds. Their color 
is either a fine saffron or ochre yellow, brick red or dark brown, 
or they are whitish and chalky, with a yellowish or a greenish color 
on the outside or in layers internally. The larger ones are rounded 
or oval in form and in section they show a laminated structure ; or 
they are from mutual pressure faceted and polyhedral because of 
their softness. 

Their composition varies. From analyses made by Maly, Phip- 
son, Hermann, of the gall stones of cattle, these concretions were 
found peculiarly rich in bilirubin or the compound of bilirubin with 
calcium (28-61 per cent.) and poor in cholesterin (only 1.35 per 
cent. ; according to Zschokke, 10-15 per cent.) . E. Voit found in a gall 
stone of a horse but little biliary pigment, no cholesterin, large 
amounts of biliary acids, and in the ash chiefly calcium phosphate. 
In the large examples not infrequently food particles (bits of cereals 
or of hay or straw) are present, apparently forced from the intestine 
into the widely dilated and relaxed biliary canal (peristalsis).* 

The origin of gall stones is not as yet entirely clear. Accord- 
ing to Naunyn the mucous membrane of the gall passages in 
catarrhal conditions produces a secretion rich in calcium salts, and 
at the same time albumen is exuded into the bile. The presence 
of the albumen favors the precipitation of the lime, and the increased 
proportion of bilirubin may be explained by the thickening of 
the bile from retardation of its flow. [The solid pigmentary sub- 
stance in gall stones is a definite chemical combination between 
calcium and bilirubin, the latter having feeble acid combining 
powers.] 



♦Occasionally in swino and deer accumulations of ordinary sand (silicate and 
quartz fragments) have boon found, which could not possibly gel into (ho biliary 
passages except from duodenal contractions, 



224 



Retrogressive Processes. 



Cholesterin gall stones are apparently the result of a pathological 
secretion from the biliary mucous membrane ; according to Gamgee, in 
cholecystitis there may be observed myeline-like masses in the epithelial 
cells, a lumpy, glistening substance, which floats on bile and which, on 
the addition of acetic acid, crystallizes as cholesterin. These cholesterin 
clumps are regarded as the stage preceding the deposition of cholesterin 
for the formation of calculi (Naunyn). 



7. 




Fig. 37. 
Gallstones from cow. (After Trolldenier. ) 



It has been pointed out, too, that colon bacteria or a mixed 
infection penetrating from the intestine may set up a cholangitis 
and cause disintegration of the secretion and exudate and in this 
way give origin to calculus formation (Halia, Naunyn). 

The presence of biliary concretions may produce no symptoms as 
long as the bile is able to flow without interference ; but at times 
by obstructing the biliary passages they cause biliary stasis and 
jaundice or, by involvement of the cystic duct, retention of the 
mucus in the gall bladder with marked dilatation of the latter 
(hydrops vesicae fellece). These calculi with their bacteria and 



C oncrement Formation. 



225 



particles of food within them may excite inflammatory changes, and 
give origin to biliary colic from the spasm and inflammation of the 
muscular wall of the bladder ; and it is possible that rupture of the 
latter may occur. 

Salivary Calculi {calculi salivales). — Small concretions and cal- 
culi are formed from the calcium salts of the secretion (calcium 




Fig. 38. 
Sectioned surface of a gall stone of a cow. 



(After Trolldenier.) 



carbonate and phosphate) and from carbonate of magnesium, potas- 
sium and sodium in the ducts of the oral salivary glands (parotid, 
sublingual and submaxillary) and of the pancreas (abdominal 
salivary gland). These concretions are usually chalky. In the 
horse salivary calculi sometimes form in Steno's duct to the size 
of a goose egg (200 to 600 grams in weight), often Having as a 
nucleus a bit of chaff, a piece of straw or an oat seed, which has 
in some way gotten in from the mouth. According to Gulippe 
bacteria by inducing fermentative changes in the saliva seem to 
be the occasion for the separation of the salts. 



226 



Retrogressive Processes. 



The larger calculi cause distension of the passages and retention 
of the secretion. The earthy salts of the saliva may also precipitate 
in the mouth cavity. Mixed with desquamated epithelium and 
oral vegetable organisms they accumulate as hard, brittle, dirty- 
white deposits, particularly about the neck of the teeth, forming 
the so-called tartar (common in dogs, rare in horses). 

Intestinal Calculi. Fecal Concretions. — Indigestible parts of 
the food and earthy substances with them sometimes accumulate 
in the large intestine in more or less compact masses, 
which may have important consequences upon and menace the 




Fig. 39. 
Vegetable concretion from the colon of a horse. 



health of the animal. In the dog, more rarely in the cat, bone frag- 
ments in the fecal material, forming in hard, dirty brown to black 
sausage-shaped masses, and perhaps reaching the thickness of the 
human arm, are quite likely to block up the rectum and colon and 
cause erosion and necrotic ulcers of the mucous membrane, obstruct- 
ing all the rest of the intestinal contents, and producing fecal 
fistulae and rupture of the intestine. In horses concretions made up 
of vegetable fibres are often formed in the caecum and colon, com- 
pressed into ball-like clumps, sometimes attaining the size of a 
human head, and more or less encrusted with mineral matter 
{phytoconcrements x mixed concrements) , 



Concrement Formation. 



227 



In the parts of the large intestine just mentioned there are also 
found not infrequently hard, stony concretions {intestinal calculi, 
enteroliths) , ranging in weight up to eleven kilograms, looking 
not unlike billiard balls or bowling balls, or sometimes of pyramidal 
shape from being worn off on the sides. The main constituent of 
these dense calculi is, according to Fiirstenberg and Gurlt, ammonio- 
magnesium phosphate (over ninety per cent.), the precipitation of 
which occurs especially in feeding wheat and rye bran (the horses 
belonging to millers and bakers), such a food containing a large 
amount of magnesium phosphate. This is dissolved in the acid 
intestinal juice and in case of the development of ammoniacal com- 
pounds unites with the ammonia to form the almost insoluble triple 




/ I'*, . ; ''iVj'V, . ,','tf:*: 



: 





Fig. 40. 
Half of a fractured lamellated enterolith from a horse. 

phosphate. The marked sluggishness of peristalsis which obtains 
with this diet, and ammoniacal fermentation of the intestinal con- 
tents by bacteria, aid in the formation of the calculi. Usually the 
larger examples are single ; but of the smaller sizes there may be 
dozens or hundreds in one intestine. In addition to pressure ero- 
sions caused in the mucous membrane by these calculi, they may 
produce fatal results, especially by accidental impaction and ob- 
struction at some narrow part of the intestinal tube. (For details 
cf. Spezielle pathol. Anatomic d. Haustiere, II. Aufl. 1902, Stutt- 
gart, Enke's Verlag.) Horses which take in sand and mud in 
drinking from pools (and the same is true of hogs from swallowing 
ground while rooting) occasionally get Large masses of such ma- 
terial into the intestine and ma\ as a result suffer from the forma- 
tion of diverticula. 



228 



Retrogressive Processes. 



In pigs bristles which are swallowed may be massed together 
in the intestine by the peristaltic movements into cylindrical bristle 
balls; in ruminants hair which has been swallowed may form in 
the abomasum one or more spherical, felt-like bunches, and in the 
same way remnants of plant fibres may also be compressed into 
similar balls here (piliconcrements, phytoconcremcnts, bezoars). 




Fig. 41. 
Cut surface of half of an enterolith from horse (one-half reduced). 

Pus concretions result from the inspissation of pus retained in 
old abscesses and other places, possibly with more or less calcifica- 
tion. In the air chambers of horses they are met quite commonly, 
supposed to be due to the compression of thick streptococcus pus 
by muscular pressure (movements of chewing and swallowing), 
often into chestnut-like or potato-like masses. In cattle tubercu- 
lous caseated masses in bronchiectatic cavities may form hard 
lumps, perhaps reaching the size of a fist. 



Gout. 



229 



Gout. 

This name is applied to a disturbance of metabolism characterized by 
accumulation and deposition of urates of the alkalies in the tissues, the 
joints being special seats of uratic deposits, and developing painful nodular 
swellings (gouty nodes; tophi, from rb<p os, cretaceous stone). In man 
this is a common affection, but a rarity among mammalian animals. 
Only one case is on record (Bruckmiiller) in a hunting dog. (In two 
published cases in swine [Virchow, Mendelsohn] there was not a deposi- 




Fig. 42. 
Pus concretions from an air chamber of horse (reduced one-half). 



tion of urates, but it would seem that the whitish, chalky masses found 
in the joints were composed of guanin, or, according to Voit, of ty rosin.) 
Genuine gout, however, is common in pigeons, chickens, parrots, ostriches, 
and is quite frequent in birds of prey (Kionka) ; it has been observed, too, 
in reptiles (alligators, snakes). 

The symptoms of avian gout manifest themselves by progressive weak- 
ness of the bird, with loss of appetite and emaciation. The legs present 



230 Gout. 

more or less prominent arthritic swelling and are unfit either for standing 
or walking. Sometimes there is also a swelling of the wing joints, and 
in case of chickens, a strong bluish-black discoloration of the comb becomes 
apparent. At autopsy of birds dead from the affection after a course 
of some weeks or months, there is at times found within and about the 
joints a deposit of white, chalky, mortar-like material; and the serous 
membranes (membranes of thoracic and peritoneal air chambers and peri- 
cardium), the epicardium and the liver are apt to be found the seat of 
similar deposits, as though powdered with plaster of Paris. The kidneys 
are thickly beset with white points and sometimes the ureter is completely 
filled with white plugs. Microscopic examination shows the condition 
to consist of a deposit of and infiltration with crystals of sodium urate 
(plates and needle-shaped crystals grouped in stellate bunches). 

As far as the causative conditions and nature of the metabolic dis- 
turbances, fundamental to the affection, are concerned, but little has been 
definitely established in case of human beings. Practically all that is known 
is that certain kinds of food (large amounts of albuminates, highly sea- 
soned meats [meats rich in nucleo-proteids], alcohol), lead-poisoning and 
a predisposition of the individual play a part. It has been established 
in case of avian gout, by the highly interesting investigations of Ebstein, 
Kionka and Kossa, that a number of poisons which injure the renal 
tissue and, too, exclusive meat diet are capable of inducing in experimental 
cases the characteristic features of gout. As early as 1766 Galvani pointed 
out that chickens became gouty after ligature of both ureters, an ob- 
servation which has been repeated by Zaleski, Colasanti, Schroder and 
others. Ebstein injected subcutaneously in chickens neutral chromate of 
potassium in separate doses of 0.32 gram, with the idea of impairing the 
excretion of uric acid by producing serious renal lesions ; with this dosage 
the birds lived for some weeks, and, as a matter of fact, Ebstein estab- 
lished that they undoubtedly became gouty. The same results were obtained 
by v. Kossa in chickens by intramuscular injections of solutions of oxalic 
acid, phenol, acetone, aloin, corrosive sublimate and, too, cane sugar. 
Kionka drew attention to the fact that carnivorous birds are the ones 
which are especially subject to gout, and from a series of studies estab- 
lished the fact that chickens on exclusive meat diet (160 grams a day), 
to which they may become accustomed, may become gouty in the course 
of a few weeks or several months and then die of the affection. The 
large, heavy breeds showed greater tendency in this direction than the 
commoner small chickens. There were noted a great increase in the 
production of uric acid with this diet and a correspondingly high dis- 
charge of uric acid (8-9.5 grams each day) and of nitrogen (3-4-5 grams 
a day) in the excreta. Since M. Kochmann has shown that in dogs, also, 
when fed exclusively with horse flesh, the renal and hepatic parenchyma 
suffers a change (parenchymatous nephritis and hepatitis), and the poisons 
above mentioned give similar results, v. Kossa looks upon the nephritis 
as the cause of the toxic gout interfering with the elimination of urates 
just as if the ureters were ligated. Under natural conditions almost every 
chronic nephritis in birds may be followed by gout. Ziirn once observed 
the affection after feeding ustilago maidis to chickens. The common 



Gout. 231 

occurrence of the disease in birds of prey kept in captivity and having 
insufficient exercise, favors the view that muscular activity lowers the 
disposition, or, in other words, uric acid is destroyed in the working 
muscles. The difference, not merely in diet, but in the possibility of 
destruction of uric acid in the muscles, liver, kidneys and spleen are 
probably reasons for the rare occurrence of gout in mammals and the 
fact that it is never seen in herbivora. 

[In man the affection, characterized not only by the joint changes, but 
also by widespread sclerotic lesions, especially of the arterial system, is 
referred to uric acid and certain precursors of this substance, the purin 
bodies. These are particularly the products of metabolism of nucleo- 
albumens, and much importance is ascribed to diet rich in these albumi- 
nates, young meats, pancreas, liver, etc. Other factors, as insufficient 
exercise, etc., are also deemed important.] 



PROCESSES OF REPAIR AND NEW FORMATION 

Regeneration. 

By the term regeneration is meant a process of new formation 
of tissue which occurs in connection with tissue loss, replacing such 
loss and then ceasing. 

Renewal by metabolism of the functional capability of cells 
remaining alive after fatigue and exhausting diseases is known as 
recovery or reconstitution. In the living organism cellular material 
is being continually used up and in consequence there are always 
some cells being destroyed and new ones growing to take their place. 
The cellular covering of those surfaces which are in relation with 
the external world and from which the cells are loosened by 
mechanical influences (epithelium of the skin and mucous mem- 
branes), is especially subject to continual losses and compensation 
for such losses by a succession of new cells. In the glands, too, 
there is apparently a continual change of old and new cells, as the 
function of the gland cells cannot but occasion in them aging and 
death; this exchange is an active one in the tissues of the testicles 
during the period of seminal production, and in the ovary, too, the 
formation of ova is in a measure a regenerative production. In 
some glands which form their secretions without particular destruc- 
tion of their cells (mammary glands, kidneys, sweat glands), 
renewal in this sense is, however, not recognizable ; and in case 
of the important elements of the central nervous system, the 
ganglionic cells, it is a question whether they are at all subject to 
change or persist throughout the whole life of the individual. 

The cellular constituents of the blood and lymph are very perish- 
able, and in the spleen, bone marrow and lymph nodes compensatory 
production of these corpuscles is unceasingly going on. 

A regenerative process may be regarded as pathological only 
in the sense that it occurs in connection with unusual losses of 
substance or pathological lesions of tissues, as after ruptures in 
continuity ; it is in reality only an exacerbation of physiological 
histogenesis as the processes of growth in both are identical. 



Reasons for Regeneration. 233 

The causes, or better, the reasons why, after tissue injuries and 
losses, regenerative growth occurs, are complex. Normal increase 
of cells depends upon inherent peculiarities of the cells themselves. 
The capacity for multiplication is characteristic of all cells for a 
certain time after they are formed ; it is most active during em- 
bryonic life and in youth, diminishing and, within certain limits, 
ceasing after the full development of the body, as determined by 
the relative tension of the tissues and the inherited characteristics 
(phylogenetic). From those influences exerted by the tissues upon 
each other and by which mutual restraint is maintained so that 
an overgrowth of one cannot take place at the expense of the rest, 
the normal inter-resistance of tissues, the so-called tissue tension* 
takes its significance. (However, as Marchand has suggested, 
mechanical resistance to growth does not alone explain tissue 
equilibrium ; there are other participating influences, as nutrition. 
The constancy of the shape and size of the organs and the cells is 
a fundamental peculiarity of the species.) 

We may see in many cases where removal of normal tissue 
resistance has taken place (where, for example, the tissue tension 
has been released by the formation of cavities) the parts bordering 
on such situations assume active growth. This is very strikingly 
apparent where there is a cleft in the diaphragm next to the liver, 
as the result of which the liver tissue invariably grows through the 
round or oval diaphragmatic opening into the chest cavity (as a 
button goes through a buttonhole), the otherwise uniform opposi- 
tion which the diaphragm exerts upon the anterior surface of the 
liver being interrupted at this position and lost. In any defect 
produced by trauma or analogous loss of continuity of the tissues 
the normal resistance is more or less lowered and the adjacent cells 
are able to penetrate into the vacant space and fill it (vacuum 
growth). As a result of the displacement of the cells thus pene- 
trating the vacant area from their original station, space is afforded 
in the latter position as well, thus giving opportunity for further 
proliferation of the elements persisting there (Ribbert). According 
to Ribbert the displacement of cells even from distant positions 
may be explained by such a release of tension ; thus in the regenera- 
tion of blood, leucocytes pass into the circulation and spaces are 
left in the bone marrow, which are filled by newly forming cells. 
and with the passage of these the process repeats itself indeti- 

* Ribbert means by tissue tension not only pressure conditions, but all the 

opposing inlluenees of the various tissues upon each other, 



234 Regeneration. 

nitely. Anything, even hyperemia, which tends to separate the 
tissues, has in Ribbert's opinion the same effect to decrease tension 
and produce space. Although objection may be made that the dis- 
tending cause must also have a pressure effect which should inter- 
fere with growth, it must be granted that the vessels distended 
and engorged in hypersemic conditions separate from each other 
the closely packed cells, and that similarly the filling up of the 
lymph spaces with exuded material forces the cells apart and in 
this sense has an influence to relieve tension. The release of 
mechanical tension is, however, not invariably the only cause of 
tissue growth; there are other factors which are operative to di- 
rectly stimulate cellular proliferation. There can be no doubt that 
increase of nutrition, provided the cells are in condition to 
assimilate it, must necessarily favor multiplication. Especially in 
inflammatory regeneration it may be appreciated that there is such 
a rich nutritive supply possible for the cells at the periphery of 
the inflammatory focus from the albuminous fluid exudates, fibrin 
and products of disintegration of leucocytes and blood coagula., 
that there cannot but coexist a condition of extra nutrition of 
these elements along with relaxation of and space formation in 
the tissue. The multiplication of tissue in chronic inflammations, 
protracted hyperemias and lymph congestions may also be partly 
explained by this idea. 

In addition it is possible that the elevation of temperature 
attending inflammatory processes may play a part, as it 
is well known that warmth is an important stimulus to cellular 
activity and therefore to cellular proliferation. Chemical agents 
should also be included among the important factors of stimulation 
of cell multiplication. Just as the mobile leucocytes are attracted 
by nutritive substances and other materials and assume a phagocytic 
activity, the fixed cells respond to the chemotactic stimulus of 
nutrient matter. They do not merely manifest evidence of phago- 
cytic action which underlies their hypernutrition and consequent 
cell division, but there may be distinctly recognized, as in the 
regeneration of nerves, that there exists some special substance 
exerting attraction, which determines the direction of growth of 
the proliferating cells. Fibrin especially seems to exert this two- 
fold influence ; in most cases where a layer of fibrin overlies the 
tissue, the latter is apt to soon proliferate into . the fibrin 
(Marchand). The substances set free by the destruction of leu- 
cocytes are apparently capable of exerting a chemical stimulus 



Reasons for Regeneration. 235 

in this sense. According to Marchand many cells have a tendency 
to adhere to their support with as broad a base as possible until 
forced off by other cells of the same type, as may be seen in the 
way young connective tissue cells force their way into the smallest 
cellulose meshes of elder pith, necessarily passing through its nar- 
row pores and changing their shape to marked degrees. This tactile 
stimulus perhaps explains the tendency of connective tissue cor- 
puscles to apply themselves about foreign bodies, fibrin fibrils and 
analogous objects. 

In most cases the causes enumerated are combined to give origin 
to the stimulus for cellular proliferation ; for example, where granu- 
lation tissue grows up and out of a wound in a luxurious manner 
instead of ceasing to grow after filling the wound and then 
cicatrizing, the condition may be ascribed to the combined influence 
of a number of the conditions above indicated, as the absence of 
pressure opposition, excess of nutrition and the action of special 
irritants (saliva, medicaments). 

Regenerative capacity is possessed by the cells and tissues of 
animals in varying degree. In invertebrates and the lower verte- 
brates the power of replacement or regeneration of important parts 
after loss is common to all the tissues. Both pieces of a divided 
earthworm grow into perfect creatures ; salamanders and lizards 
can reproduce completely the loss of a tail, with bones, muscles, and 
even the portion of spinal cord belonging thereto ; salamanders can 
form a new leg in place of one cut off, or an inferior maxilla 
(Samuel, Ribbert). This extensive regenerative capacity has been 
tentatively explained by the supposition that such low forms of 
animals are more commonly subjected to injuries of the type indi- 
cated and so their cells, naturally and because of their less com- 
plicated structure, retain their power of adaptation better than those 
of the higher animals. In the latter the cellular construction is 
more complicated and more fully developed for special functional 
requirements, and possess a less marked tendency to divide in 
comparison with the simple cell forms, are less independent, and in 
some degree require the co-operation of other cells in their nutritive 
processes. The more a type of tissue or cell departs from its 
embryonic state and the higher differentiation it attains, the more 
difficulty it experiences in attempting regeneration. The epithelium 
of the skin and mucous membranes and connective tissue retain 
their power of adjustment in response to the numerous faults to 
which they are liable, and easily and quickly regenerate in the 
higher as well as the lower forms of life ; but the ganglionic 



236 Regeneration, 

nervous cells and striated muscle, which can only exist, from a 
functional standpoint, in connection with nerves and which are of 
a decidedly complex structure, and in the same way glandular cells, 
regenerate only under special circumstances or not at all. 

[The conditions, then, which underlie cellular regeneration may 
be summarized somewhat as follows : Only cells which from the 
simplicity of their structure and function or from the fact that they 
have not advanced far from their embryonic state are likely to mul- 
tiply with any comparative ease. Any cell must be provided with 
sufficient nutrition to maintain its cellular activity and life if it be 
expected to divide, and extra nutrition as met in hyperemia favors 
multiplication. Cells capable of division cannot, however, prolif- 
erate if there be important mechanical or physiological opposition 
exerted by the other cells and structures of the body, and release 
of such mutual tension (mechanical, nervous, chemical) must be 
afforded before proliferation is possible. But in addition a definite 
stimulus to division should exist. This stimulus may be of chem- 
ical nature, perhaps afforded by special chemical substances coming 
to the part from previous cellular disintegration (here the brilliant 
results of Jacques Loeb in producing multiplication and develop- 
ment of unfertilized ova of sea-urchins by immersion in special 
chemical solutions are strongly corroborative), electrical (here, too, 
the work of Loeb and his associates is illuminating), thermic or 
mechanical.] 

In the adult organism of animals and birds the somatic cells 
reproduce in their process of division and multiplication only cells 
of their own type (omnis cellula e cellula ejusdem generis) ; in other 
words, a newly formed tissue is invariably the product of tissue of 
the same kind. It was formerly believed the various types of cells 
could in their multiplication produce opposite types and that in the 
same way as the various organs arise by their differentiation from 
the three embryonic layers similar transformations of tissue could 
take place in the restoration of post embryonic defects. A certain 
capacity for transformation {metaplasia) is possible in related 
types of cells and their matrix products. Thus the different 
varieties of epithelial cells may be changed by external influences 
(pressure) ; and within the group of connective tissues transforma- 
tions occur, as the formation of bone and cartilage from fibrous 
connective tissue. But connective tissue is never changed into 
epithelium, or the latter into connective tissue, the four distinct 
groups of primary tissues (epithelium, connective tissue, nervous 
tissue and muscle) never interchanging. 



Regeneration of Connective Tissue. 237 

The nature and method of cellular proliferation, as far as 
nuclear and cellular division is concerned, is in general the same as 
in normal life, although there are pathological irregularities met 
in the chromatin network and detailed structure of the protoplasm. 
The replacement of lost tissue originates from the cells which hap- 
pen to remain unchanged at the site of the defect or exist imme- 
diately about it. If there are elements present in such a position, of 
the same kind as those lost and capable of multiplication, their pro- 
liferation may completely restore the fault, the area of loss being 
filled up with identically similar elements with the same functional 
abilities (simple or complete regeneration). . Should the proper 
cells be absent from the vicinity of the faulty area regeneration 
will be incomplete (false), and the space will be occupied by cica- 
tricial tissue derived from the connective tissue structures every- 
where present. 

Regeneration of Connective Tissue and Bloodvessels. The con- 
nective tissue framework is the tissue which takes the principal 
part in repair in lesions of any kind, whether traumatic lesions of 
continuity or necrobiotic destruction of the parenchyma of organs ; 
usually the first elements to multiply being the connective tissue 
cells, these taking the place of the various elements incapable of 
regeneration. For this purpose their power of movement and of 
taking up other cells and all sorts of disintegration products 
makes them of value to the organisjn in the removal of 
substance which has become useless, and in the construction 
of a protective wall about foreign bodies. The greater 
part of the connective tissue seen in sections is made up of minute 
narrow spindle cells, almost completely occupied by dark elongated 
nuclei, and intervening bundles of fibrils. In case of prolifera- 
tion of this tissue these spindle shaped elements multiply, the 
nuclei undergoing mitotic division and the protoplasm increasing 
in volume. The newly formed connective tissue corpuscles are 
thicker and polymorphous, sometimes rounded or polyhedral, and 
provided with a number of processes ; they usually lie closely sit- 
uated, often in rows one after another, and show their active 
part in the proliferation by the presence of mitotic nuclear 
figures (one cell sometimes containing two or three nuclei). As 
they approach the type of embryonic mesoblastic cells and repre- 
sent the young germinal elements of connective tissue they arc 
known (Lebert) as Hbroplasts . (TrXda-aetu, to form), or fibroblasts 
(p\a<TTdvu), to germinate). Tn connection with the multiplication 
of these cells there also occurs a new formation of the connective 



2 3 8 



Regeneration. 



tissue fibrils, the processes of the fibroblasts splitting up into fine 
threads, at first in a brush like fashion, the protoplasm of the 
cell gradually changing completely into a bundle of parallel fibrils 
(Diirk, Neumann, Ziegler). Thus by the splitting of the enlarged 
cell-body into fibrils the cell comes to resume the type of the fixed 
connective tissue corpuscles, and the mass of proliferated fibroplastic 
tissue assumes the character of adult connective tissue structure. 
In addition to the fibrils the protoplasm of the connective tissue 
cells gives off a greater or less amount of a soft mucoid inter- 
cellular substance (Marchand). The young fibroblasts are con- 




Fig. 43. 
Fibroblasts and angioplasts in granulation tissue of horse. 

tractile and consequently are inconstant in form; they can project 
processes of their substance and thus can surround other cells, 
shreds of tissues and nutrient substances and incorporate them 
like phagocytes. They can also change their position, this property 
explaining the fact already mentioned that foci of disintegration, 
areas of haemorrhage and situations of other types of lesions are 
penetrated and occupied, and foreign bodies are encapsulated by 
these elements. Their motile power is so marked that if, for ex- 



Regeneration of Connective Tissue. 239 

ample, a bit of sponge or fragment of elder pith be introduced into 
a tissue or serous cavity it becomes completely penetrated by these 
fibroblasts. 

Along with the connective tissue cells proper, the endothelial 
cells of the blood and lymphatic vessels take part in the new forma- 
tion of connective tissue. In both forms of cells mitosis prevails 
profusely ; the young endothelial elements resulting from the cell di- 
vision are like the other fibroblasts, being distinguishable from those 
derived from the spindle cells only at their places of origin from the 
blood vessels, where they are forming capillary tubes. Whether 
endothelial cells ever form fibrils or solely develop into vessels is 
not fully determined (for details consult Marchand). Another 
long debated question, whether the leucocytes actually take part in 
the connective tissue formation and are transformed into connec- 
tive tissue cells, may be answered on the basis of more recent 
studies (Marchand) that the white corpuscles which exude from 
the blood vessels are principally concerned in the removal of for- 
eign matter and products of disintegration, that they furnish nutri- 
tive substance in case of their own destruction, but are incapable 
of forming intercellular material and therefore cannot be consid- 
ered as actual constructive elements of the connective tissue. The 
presence of these leucocytes in every area of proliferating connec- 
tive tissue is therefore dependent upon their entrance partly from 
the vessels, partly from points of lymphoid development to be 
found commonly along the bloodvessels in any tissue. The whole 
cellular group more or less closely approaching leucocytes and cells 
from the lymph glands (lymphocytes), but because of their more 
conspicuous cytoplasm or a variety of granulations of their proto- 
plasm given other names (plasma cells, mast cells, leucocytoid cells, 
polyblasts, klasmatocytes), are also found in the growing connective 
tissue. The origin of these cells and the question of their relationship 
is still rather uncertain ; probably they are all immigrants originating 
from lymphocyte depots. Giant cells (polykaryocytes) are also often 
observed in developing connective tissue, and multinucleated cells, 
especially when foreign bodies are present ; they are formed partly 
from the multiplying spindle cells, partly from endothelial cells, and 
may be regarded as cells whose protoplasm has increased and whose 
nuclei have multiplied more rapidly than cell division could keep pace 
(proliferation giant cells). According to another view they are 
caused by coalescence of closely grouped embryonic cells (congluti- 
nation giant cells). 

Opinions concerning the mode of origin of elastic fibres in the re- 



240 



Regeneration. 



generation of connective tissue are not fully formulated ; their forma- 
tion is, however, a slow process. It is only after four or six weeks 
or after several months after repair by the fibroplastic tissue that 
elastic fibrils appear in the intercellular substance ; and even after 
years these do not attain the diameter of the original elastic ele- 
ments. 

Connective tissue, modified to form adipose tissue by fatty infiltra- 
tion, is capable of proliferation to the same extent as ordinary connective 
tissue cells. The nucleated protoplasmic remnant of the fat cell undergoes 
division, and the new cells usually at first accumulate in the fat vacuole 

within the old cell membrane. 

Formation of blood -vessels takes place by a process of budding 
and division of the endothelial cells from the existing capillaries. 
The protoplasm of the endothelial cells in the walls of the old ca- 
pillaries which have remained intact send out pointed., conical proc- 
esses, which lengthen out in thread like manner, and penetrate 




Fig. 44. 

Vascular sprouts, highly magnified: (after ITioma 1 . The long thread-like ends 
of the sprouts are only partly reproduced. 

between the proliferating fibroblasts. Coincidently mitosis of these 
endothelial cells takes place and at the base of the bud cellular 
division begins and the endothelial cells (angioplasts) proliferate. 
These new elements lie alongside of each other and fuse, with their 
often curved and reticular branches, into solid cords of cells. 
From these the capillary tubes are produced by the forcible pene- 
tration of the blood from the old vessel in between the dividing 
endothelial elements, thus making a space filled with blood. This 
proceeding at all places where these buds are forming, gradually 
the whole network becomes canalized. From some of the capillaries 
arteries are formed, from others veins, the lumen of the tubes 



Formation of Blood Vessels. 241 

being widened by blood pressure and growth of the wall (increase 
of surface by multiplication of the parietal endothelial cells) ; 
smooth muscle growing from the existing arteries into the newly 
formed vessels, and the surrounding fibroplastic tissue aiding in the 
formation of elastic fibres. (Regeneration of blood vessels has 
been especially studied by J. Arnold, Jos. Meyer, Billroth, C. Weil 
and Thoma.) 

The development of angio-fibroplastic tissue is accompanied by 
more or less manifest phenomena of inflammation (hypersemia, 
exudation of leucocytes) and is therefore in a sense a result of pro- 
ductive inflammation. Depending upon the number of blood ves- 
sels present and the relative amount of proliferated connective tissue 
the new structure presents a reddish-gray, grayish-white or pure 
white, swollen appearance, semitransparent and of a shape conform- 
ing to that of the lesion which it has followed. When it develops 
diffusely, as in parenchymatous organs, to replace destroyed gland- 
ular tissue, it gives rise to more or less marked induration of the 
part (indurative inflammation), or forms translucent hard thicken- 
ings (in fasciae, serous membranes), bands of adhesion (adhesive 
inflammation) and sometimes villus-like fringes. In focal devel- 
opment it forms white trabecular or nodular connective tissue 
masses (in infarcts of the kidney) ; as the result of a demarcating 
inflammation about some blood clot or foreign body it constitutes 
a connective tissue capsule. On the free surfaces of wounds the 
new formation is seen as a finely granular soft tissue, producing an 
exudate, with a deep red or reddish gray color from the abundance 
of capillary buds in its structure ; it is known as granulation-tissue. 

All fibro-angioplastic tissue is at first likely to form a greater 
bulk than the lesion which it replaces. There exists an excessive 
production of the young cells and these cause an excess of inter- 
cellular material. With restoration of normal tissue tension and 
maturation of the growing tissue, these originally enlarged cells 
shrink and the intercellular substance decreases ; the fibrils are ar- 
ranged in a parallel fashion from the tension and pressure of the 
neighboring structures influencing them ; some of the capillaries 
become obliterated, that is, narrowed, from pressure by the shrink- 
ing fibroplastic tissue. In this way, too, the whole tissue, some- 
times, because elastic tissue is produced in deficient amount or not 
at all, becomes dense and bard and is changed into cicatricial tissue. 
This is apt to contract still further, thus forming in the surface of 
the skin and organs depressions or indentations of radiating stellate 
form. 



242 Regeneration. 

Regeneration of Epiderm and Epithelium of Mucous Mem- 
branes. — The epithelium on the surface of the skin and mucous 
membranes is capable of very rapid and complete regeneration. 
Because of the continual loss of cells from desquamation as they 
grow old the tissue is always prepared for and actively engaged in 
regeneration. Either because of cellular tactile irritability (v. p. 
235) or because the removal of tissue resistance in defects mechan- 
ically causes it to undergo a regressive development, the new tissue 
is very apt to spread out upon the free surfaces and to some extent 
to increase in volume, a flat cell thus arising from a cylindrical cell 
at the border of the lesion. The new cells are always formed from 
existing epithelium and can only be produced providing vitally 
capable cells of the same tissue are present in the vicinity of the 
lesion. 

The formerly accepted belief that epithelial cells could develop from 
connective tissue has been shown to be erroneous. 

In case of superficial loss of epithelium (abrasions, epithelial ne- 
croses) the new surface cells grow over the denuded papillae from 
the margin of the surrounding epiderm. Within three-quarters 
of an hour after a wound has been inflicted, under the microscope 
there may be observed enlargement of nuclei and direct and indi- 
rect nuclear division in the cells of the stratum Malpighii, both in 
the margins of the lesion and at some distance from it; after eight 
or ten hours the epidermal border is visibly thickened; and small 
lesions only a few millimeters in circumference may be covered by 
several layers of epithelium in the course of forty-eight hours. 
The epithelium actually spreads over the surface of the wound, 
either from active motile power or because the superficial cells are 
dislodged by those growing back of them in the deeper layers. 
If the part deprived of epithelium is covered by fibrin, blood or pus, 
a granulating surface, the proliferating epithelium at the margin 
forces its way beneath the coagulated crust over the cicatrizing 
connective tissue ; in these cases the epithelial layer is often rid- 
dled with leucocytes, and afterward in the clefts and spaces thus 
produced new cells may grow, forming branched plugs made up of 
concentrically laminated, keratosed, epidermal balls (horny pearls, 
atypical epithelial proliferation of Friedlander) . Occasionally the 
epithelium may penetrate along fistulous passages ; as in a perforating 
dental alveolar fistula (horse) the squamous epithelium may grow 
through the alveolus from the mouth into the nasal cavity.* 

* Penetrative growth of epithelium at the border of ulcers and fistulas 
may determine a free atypical new formation of this tissue and thus give 
rise to cancer. 



Regeneration of Epithelium of Cornea, Hair, Hoof. 243 

The advancing margin of the epiderm may be seen as a bluish 
white wavy, zone, sometimes with a rosy tint from the hypersemic 
substructures showing through. Sometimes in addition to the epi- 
dermal growth at the margins of the lesion, islands of epithelium 
may be observed in the midst of the new surface. These may origi- 
nate from the remnants of the ducts of sweat glands or hair folli- 
cles (the cells of which are practically identical with those of the 
surface) which were left intact because of the superficial extent 
of the loss of substance ; or may arise from epithelial cells separated 
from the border and caused to adhere to the surface of the wound 
by the application of a bandage. 

The proliferation of the epithelium does not stop until the free 
surface of the lesion is completely covered. Epithelial scars are for 
a long time devoid of pigment and in a dark skin the cicatrix is 
conspicuous because of its whiteness. 

The corneal epithelium is very quickly reformed after destruc- 
tion, a circular loss of three millimeters diameter being perhaps re- 
placed in the course of from thirty-six to forty-eight hours. The 
cells at the margin, moving in by amoeboid power and flattening out 
to form at first a protective single celled layer, spread out over the 
surface ; these multiply, showing mitotic figures and multinuclear 
examples, and build up the layers of corneal epithelium ; the cells 
assume a cuboidal shape and the lesion is completely repaired. In 
case of wounds of deeper extent or those perforating the whole 
thickness of the cornea and involving the corneal connective tissue 
and Descemet's membrane, the lesion is at first filled up by fibrin 
(from the aqueous humor). The rapidly growing epithelium ex- 
tends over this and forces itself into the depth of the wound like 
a plug. The connective tissue is formed subsequently, and on the 
posterior surface the endothelium of Descemet's membrane regen- 
erates its single layer of cubical cells. A milk white spot remains 
at the site, the result of cicatricial production by the newly formed 
connective tissue. 

(Regeneration of the cornea has been exhaustively studied, especially 
from an experimental standpoint, in animals; for details cf. Marchand.) 

Regeneration of hair can occur only in case the hair follicles 
or portions of them remain. In all deep cutaneous lesions the cica- 
trix is permanently smooth and devoid of hair. 

Regeneration of horny tissue of the hoof. After injuries to the 
keratous envelope or after it has been ruptured from suppurations 
of the corium the horny layer may be regenerated by proliferation 



244 Regeneration. 

of the keratogenous cells over the surface of the granulating papillae 
and fleshy laminae of the persisting cutis (the latter the seat of 
compensatory and sometimes regenerative changes) and the forma- 
tion of a new protective layer over the denuded papillary surface 
(Gutenacker). The first formed cells are pushed forward by suc- 
ceeding new growth and form keratous tubules by arranging them- 
selves in circles about the papillae ; later interpapillary keratous 
substance is deposited in the intervals between the tubules as a yel- 
low, perhaps soft and incompletely keratosed, and usually very 
thick mass (cicatricial keratin). In parts where there are no 
papillae the keratogenous cells are arranged in irregular, superim- 
posed layers. Operative denudations of the corium of the hoof 
from five to ten square centimeters in area may be completely over- 
grown by new horny substance in the course of from four to six 
weeks. 

(For details cf. Lehrb. d. Chirurgie, by Frontier, and Hufkrank- 
heiten, by Gutenacker.) 

Regeneration, compensatory for losses of cylindrical epithelium 
upon mucous membranes, proceeds in the same way as the process 
in the epiderm. The epithelial cells growing in from the periphery 
over the surface of the lesion at first assume flat, then cubical and 
finally cylindrical shapes and in appropriate cells it is even possi- 
ble that the ciliated border will be reformed. The surface epithe- 
lium of a wound of the gastric mucous membrane of a dog may be 
completely reformed in from four to ten days. 

Regeneration of Glands. — Epithelium of glands is very irregular 
in its regenerative ability. The epithelium of glands of the mucous 
membranes corresponds histologically with that of the surface of 
the membrane, as in the intestine or uterus ; and therefore in these 
parts epithelial repair over cicatrices, ulcers and wounds may. be- 
sides merely covering the surface of the lesion, sometimes also ap- 
parently attempt gland formation in points of depression. The 
epithelial cells formed in such cases grow from remnants of in- 
volved glandular structures or from the uninvolved adjacent tissue 
over the seat of the lesion. The depressions occur at the 
expense of the young growing connective tissue or granula- 
tion tissue which is being developed at the same time ; but the more 
marked the retraction of the scar the less successful the glandular 
reformation. Ponfick, Gluck and v. Meister in their interesting ex- 
periments have pointed out in connection with regeneration of 
the liver that after operative removal of a portion of the hepatic 
tissue from rabbits, rats and dogs a remarkable regenerative activity 



Regeneration of Glands, Spleen, Lymph Glands. 245 

occurs. After ablation of half of the bulk of the organ new liver 
tissue developed from the remaining portion by luxuriant prolif- 
eration of the hepatic cells, setting in as early as the third to the 
fifth day; after an average of from forty to sixty days the part lost 
was completely restored in volume and weight. It is conceivable 
that after other local lesions liver tissue may regenerate, yet after 
traumatic lesions or destruction of hepatic parenchyma by the pene- 
tration of parasites nothing but cicatricial connective tissue is seen 
at the site of the defects, always containing on microscopic examina- 
tion decidedly proliferated bile ducts, but without evidence of 
formation of functionally capable liver cells. This probably 
is due to the fact that in the type of defects under con- 
sideration the connective tissue framework has also undergone 
pathological changes, and perfect restoration of functionating 
parenchymatous cells can only be expected when the connective 
tissue basic structures are in normal condition (Ribbert). The 
enormous enlargement of the liver sometimes seen in tuberculosis 
and echinococcus disease is apparently due not merely to the 
foreign elements and to connective tissue hypertrophy, but may 
possibly be dependent upon a vicarious hypertrophy or regeneration 
of the hepatic parenchyma. 

It is not certain in case of the kidney whether epithelial cells 
lost in consequence of inflammations and degenerations of the paren- 
chyma can be restored completely. Lesions from infarction, suppu- 
ration or trauma always heal by cicatrization. There may, how- 
ever, take place a compensatory hypertrophy of adjacent tubules 
and glomeruli to occupy the space caused by shrinkage of such 
scars, which in a measure may compensate for the lesion. 

The tissue of the testicles and ovaries has but little regenerative 
power; space caused by trauma and degeneration is always filled in 
by cicatricial tissue. On the other hand the glandular epithelium 
of the mammary gland, thyroid, salivary and lachrymal glands is 
capable of extensive proliferation from remaining portions of the 
alveolar tissue, with formation of new ducts and glandular acini 
lined with secreting epithelium. 

The spleen and lymph nodes although subject to continual 
change of their cellular constituents and capable of originating in 
pathological conditions a marked excess of their lymphoid tissue, 
do not regenerate after traumatic lesions, being invariably subject 
to cicatricial repair. 

Striated muscle, when the fibres have been partially destroyed 
by degeneration of their substance, is able to regenerate in a certain 



246 Regeneration. 

measure; at least microscopically proliferation of remnants of nu- 
cleated sarcoplasm may be observed, whole chains or rows of new 
nuclei being produced by direct nuclear division, these in asso- 
ciation with proliferation of the sarcoplasm by longitudinal divis- 
ion going to form the so-called muscle cylinders (Waldeyer) and 
lateral off-shoots known as muscle buds (Naumann). Apparently 
the sheath of the sarcolemma develops from the surrounding con- 
nective tissue, which is also proliferating; and the developing sar- 
coplasm takes on a fibrillar structure. In traumatic lesions connec- 
tive tissue formation predominates, the healing of the wound usually 
giving rise not to the reconstruction of the contractile elements, 
but to the formation of dense scars. 

Smooth muscle even in traumatic lesions exhibits active mitosis, 
and multiplication of the muscle of the blood vessel walls is to be 
observed in granulating tissue ; but in lesions of muscular tunics, 
as of the stomach, intestine or uterus, complete restitutio ad inte- 
grum has never been observed, scar formation taking place instead. 

Regeneration of tendon tissue (studies of this process being 
often afforded in the rather common performance of tenotomy) 
begins, according to Marchand, principally from the loose cellular 
tissue between the bundles of tendon fibrils. This formative ma- 
terial, composed principally of spindle cells, develops (by mitosis) 
into the cleft between the cut ends of the tendon, which is filled up 
with blood or exudate, and unites the tendon stumps as a soft gray- 
ish fibroplastic mass. Later the fibroblasts form a fibrillar matrix, 
the fibrils arranged parallel with each other, and the tendon scar 
gradually acquires great firmness. According to Paget a divided 
tendon of Achilles of a rabbit may be found united as early as from 
three to five days and in ten days may be of sufficient strength to 
require a tensile force of twenty-eight pounds to tear it apart. 

Lesions of cartilage, as that of the air passages, the auricle, or 
ribs, are restored by connective tissue formation from the perichon- 
drium, the cells of which give origin to a fibrillar, collagenous sub- 
stance. The latter may become homogeneous and by a metaplastic 
process the connective tissue thickening be converted into hyaline 
cartilage ; and it is possible that by an infiltration of calcareous 
salts ossification of the embryonic tissue occupying the space of 
the lesion may ensue. The cartilage itself takes no part in the 
process of restoration and connective tissue scar formation is usually 
but slight. 

New formation of osseous tissue after fractures and operative 
lesions arises exclusively from the periosteum and bone marrow 



Regeneration of Bone. 247 

and ends by complete restitution of the most dense osseous sub- 
stance. The special bone cells embedded in a dense solid calcined 
matrix are unable to take part in the construction of new tissue 
because they have no space for any activity. The osteoblasts of 
the periosteum and marrow, the bone forming cells, are connective 
tissue cells which possess the peculiar ability of giving origin to an 
intercellular material with an affinity for lime salts or of them- 
selves producing calcification of the matrix and thus supplying the 
basic osseous material. They are, however, also capable of produc- 
ing fibrillar connective tissue and may act precisely as fibroblasts; 
and finally may become transformed into cartilage cells, form a 
homogeneous inter-cellular material and remain in the lacunae 
within the latter. In bone repair therefore there is first noted a 
fibroplastic callus which becomes partly changed into cartilage and 
later into calcified osseous tissue. Coincidently the blood vessels of 
the bone proliferate, complete analogy to the vascularized fibro- 
plastic callus existing in the healing of lesions of the soft parts. 
The name callus is applied to the whole of the tissue arising in the 
osteogenetic process, its origin giving the basis for differentiating 
between periosteal and myelogenous callus; that portion which de- 
velops between the separated fragments is known as the intermed- 
iate callus. 

In the neighborhood of the seat of fracture all of the periosteal 
and marrow cells and vascular endothelial cells become swollen, nu- 
clear division actively proceeds, and cellular proliferation is so lux- 
uriant that the capillaries are often found occluded by young endo- 
thelial cells and giving ofT profuse vascular buds ; the whole cellular 
callus forming a growth decidedly exceeding the diameter of the 
bone itself (the widei the space between the bone fragments the 
greater this mass). 

This callus, at first consisting of connective tissue and some- 
times called the provisional callus, has to do with the removal of the 
clotted blood occasioned by the fracture and other tissue remnants, 
even of small splinters of bone (the limy material of which is dis- 
solved by the proliferating cells), through phagocytic cells originat- 
ing from its newly forming constituents. It has a bacon-like, cartilag- 
inous appearance, surrounds the ends of the bone as a thick girdle, 
occupies the medullary cavity at the level of the fracture and the 
whole space between the broken ends. The newly formed material 
is markedly in excess, and after calcification the osseous scar unites 
the fragments as a clumsy, thick enlargement of the shaft of more 
or less spindle shape. With calcification, which renders the callus 



248 Regeneration. 

hard like ivory and of the compactness of cortical bone, the osteo- 
blasts in the provisional callus are gradually enclosed in the calci- 
fying matrix and shrink into the spindle-shaped and stellate form of 
bone corpuscles ; the newly formed vessels with their contained blood 
persist in the calcifying osteoplastic tissue, giving an analogy to 
the system of the Haversian canals of bone. There is, however, no 
lamellated structure in the tissue. After the osseous scar has become 
hard and the bone is again strong enough to sustain weight and 
muscular strain, a reduction of the excessive callus sets in, aplana- 
tion of the callus; the external bulging of the bone diminishes; the 
periosteum becomes closely adherent; the medullary callus becomes 
porous, the medullary canal opens and the medullary substance be- 
comes full of fat. These changes in the callus are brought about 
by the growth of blood vessels into it from the marrow, and by 
the influence of multinucleated giant cells of the medulla known as 
osteoclasts (K\a<r<retv, to break) because of their agency in breaking 
down osseous tissue (Rindfleisch). The shrinkage is explained by 
the biological law that lack of use causes structures to become 
atrophic, only functionating parts being maintained. Hence in 
conformity with this rule only those portions of the bony tissue 
which are required to sustain weight or to oppose strain persist as 
compact structures. 

It is well known that the texture of any bone shows an arrange- 
ment of its osseous trabecula conforming to the mechanical forces 
acting upon it; this functional adaptation is operative as well as all 
pathological conditions which occasion new mechanical features. In 
the regenerated bone tissue the resumption of function not only 
assures the maintenance of the osseous scar, but in addition de- 
termines the precise arrangement of its osseous trabecula by fur- 
ther thickening of those portions which are most heavily taxed ; the 
direction of the trabecular adjustment develops in correspondence 
with the lines of stress determined by their functional relations in 
supporting the body weight and opposing muscular strain. 

Regeneration of Nerves. — Peripheral nerves severed from their 
connection with the central nervous system by section, contusion 
or other destructive lesion, degenerate from the point of the lesion 
centrifugally to their peripheral end fibres, their axis-cylinders and 
medullary sheaths being destroyed (broken down into myelin and 
fat droplets) ; but the neurolemma and its nuclei remain intact 
(Nasse, Waller, Lent, Benecke and others). The degeneration 
may also extend centrally in the divided nerve for the distance of 
one segment (to the first node of Ranvier). Conductivity ceases 



Regeneration of Nerves. 



249 



instantly when continuity is interrupted (provided there are no col- 
lateral paths). The space intervening- between the central and periph- 
eral portions is filled at first with fibroplastic cicatricial tissue ; 
but later a complete regeneration of the nerve fibres is accomplished 
and in the course of two or more months the nervous function is 
fully reestablished. This later development of the nerve fibres, as 




Fig. 45. 

Degeneration of nerve fibres after sec- 
tion. I, normal nerve fibre. II and III, 
different degrees of destruction. S, 
neurolemma sheath of Schwann, m, 
medullary sheath. A } axis cylinder, k, 
nucleus of neurolemma. L, Lanter- 
mann's constriction of the medullary 
sheath, rnt, myelin globules, a, remains 
of axis cylinder, w, proliferating cells 
of neurolemma. Partly schematic. X 470. 
(After Thoma.) 




Fig. 46. 

Growths of the axis cylinder in the 
central stump of a divided nerve. fif., 
neurolemma sheath of Schwann. m. 
medullary sheath. A, axis cylinder of 
undegenerated part of the nerve. V. 
newly formed axis cylinder. /.•, nucleus 
of neurolemma. ir, ic, proliferated 
neurolemma cells, mt, myelin globules. 
Schematic, based on an illustration from 
Eichhorst. x 476. (After Tboma.) 



indicated by the microscopic findings, which are demonstrable with 
much difficulty, may be explained in two ways. The majority of 
investigators adhere to the views advanced by Waller and Strobe. 
according to which regeneration is the result of a growth of the 
axis cylinders of the central stump, these advancing into the young 
cicatricial mass and growing beyond it, the delicate fibres oi the 



2;o Regeneration 



<v 



axis-cylinders meanwhile undergoing subdivision. It is a striking 
phenomenon in this process that the newly formed fibres of a divided 
nerve should grow into the original areas of distribution. The 
opinion most nearly explaining this assumes that the old paths of 
distribution persist as actually empty tubes, or as the neurolemma 
tubes of Schwann containing merely a softened fatty detritus, and 
that the sprouts of axis cylinder substance find here the line of least 
resistance in their penetration. It has. however, been shown that 
after resection the nerve-sprouts, in spite of the insertion of special 
interfering objects, follow along their original direction; and the 
interesting experiments of Forsmann show that the nerve stump 
will not invariably push its way into empty glass tubes which have 
been inserted but 'will on the contrary always force its sprouts into 
glass tubes containing nerve or brain substance, even if these be ar- 
ranged in the wrong direction. It seems probable therefore that 
chemctactic force, exerted by the degenerating nerve matter of the 
peripheral portion of the nerve, determines the line of extension of 
the growing nerve fibres (neurotropism). 

The force of growth: of the central stump is usually very marked. 
Vanlair succeeded in enclosing calcareous tubes, made of bone, be- 
tween the two ends of a divided nerve, and the growing sprouts not 
only found their way into the lumen of the tubes, but even into the 
Haversian canals (Thoma). Sometimes the budding axis cylinders 
form tumor-like masses in the scar tissue around the stump, the so- 
called amputation neuromata. 

As the neurolemma with its nuclei remains intact in the degen- 
erated peripheral fibres, it is possible that the formation of new 
medullary substance may arise from this source in case the new 
axis cylinders grow into these preformed paths. Proliferative phe- 
nomena in the cells of the neurolemma have been actually observed 
( Eichhorst. L. Mayer, v. Biingner). and consequently the view is 
held that this sheath, by differentiation of its protoplasm, may give 
rise in segments to the axis cylinder and medullary sheath : that 
in this way from the old sheath new nerve fibres may be formed. 
the segments then growing together to form continuous threads. 

Ganglionic cells and the massive nervous tissue of the brain and 
cord, are incapable of regeneration. It is well known from numer- 
ous experiments upon animals and studies in man in connection 
with injuries, partial ablations and other types of loss of substance, 
as from haemorrhage, degeneration, etc., that even in case the usual 



Transplantation. 251 

fatal complications do not develop such lesions do not end in 
new formation of nervous elements but in fibroplastic cicatrization. 

Regeneration of Blood Corpuscles and Lymph Cells. — The resto- 
ration of blood cells does not take place within the blood vessels, but 
originates in those organs in which normally the continual replace- 
ment of worn out cells of the blood and lymph is accomplished, par- 
ticularly the bone marrow, spleen, lymph nodes and in lymphoid 
germinal foci scattered about in various tissues. The red blood 
corpuscles develop entirely from cells of the medulla of bones and 
are nucleated when first formed; by the time they have entered the 
circulation their nuclei have disappeared. Serious or repeated loss 
of blood cells calls forth so marked a proliferation of the hsemo- 
poietic marrow tissue that the fatty marrow of the long bones comes 
to resume its embryonic character and is changed into red marrow. 
The colorless corpuscles are produced by proliferation of the leuco- 
cvtes and lymphocytes in the structures mentioned and pass out into 
the blood. 

The fluid portion of the blood is renewed by the passage of 
water and salts from the tissues into the lymph and blood capilla- 
ries. 

Transplantation. 

Some cells and tissues can maintain their vitality for some time 
after their removal from the animal body and are capable of renew- 
ing their growth if artificially implanted upon another part of the 
same body or in another animal.* Experiments in transplanation 
have been performed frequently and sometimes successfully by 
surgeons ever since the fifteenth century, for the purpose of re- 
storing denuded parts of the skin and other tissues in man ; and, 
too, the same experiments have been repeatedly performed in ani- 
mals in order to obtain theoretical grounds for operative procedures 
and explanations of pathological questions. 

It is most easily and successfully performed in lower animals. 

Born has succeeded in causing adhesive growth in pieces cut off 

from larval amphibians to take place in various ways, as of the 

head end of one larva to the tail end of another. Joest succeeded 

in uniting the opposite ends of earthworms. As interesting trifles, 

after the castration of cocks the spurs used to be often cut off and 

•Inorganic particles, ;is bits of Ivory, who or bullets, it' they get into or 
are introduced into the tissues (implantation, insert ion i may be encapsulated, 
that is, surrounded by connective tissue. Even living or dead tissues may 
be similarly surrounded, as an extracted tooth may be thus held In an alveolus 

in which It is Implanted. In transplantation, also known as grafting (French, 

greffe), there is not merely an encapsulation or adherence of the tissue 

to the structure, but in addition it multiplies in the site of implantation and 
forms part of the organic structure with the tissue about it. 



252 Transplantation. 

inserted into a split in the comb of the capon, becoming attached 
by growth in this situation (Aldrovandi, Worm, in the seventeenth 
century ; Baronio in 1804) . The spur, if engrafted when very young, 
may grow in this new and well vascularized base to become several 
inches in length ; and sometimes the central bony core grows, carry- 
ing over it a horny epidermal covering, so as to produce two spurs 
growing alongside of each other. Embryonic tissue with undiffer- 
entiated cells shows a moderate capacity for growth when trans- 
planted. Fere grafted bits of blastoderm (forty-eight hours) and 
the eyes of six to eight day chick embryos under the skin of young 
chickens and noted that the mesoblastic tissue underwent more or 
less further development to the production of small tumors (con- 
taining cartilage and in one case small feathers), which persisted for 
about a month. Such a result has an important bearing in explain- 
ing the conditions involved in the origin of tumors. 

Transplantation of tissues is more difficult in mammals. The 
possibility is best realized when the part to be transplanted can 
retain connection with its neighboring structures by a bridge, as 
where a flap of skin is twisted around and stitched to an adjoining 
part, the nutrition of the flap being at least partially maintained 
(as in the operation of rhinoplasty in man). The result in trans- 
planting unattached and completely separated bits of the corium 
and of the epiderm is not at all uniform. In this procedure, recom- 
mended by Reverdin and Thiersch for quickly obtaining an epi- 
dermal surface over large superficial wounds, which has been tested 
by many investigators, especially by Marchand and Enderlin experi- 
mentally, the transplanted fragments adhere by a layer of coagulated 
blood and lymph to the fresh or granulating wound. Later on there 
occurs an active vascular and cellular proliferation in the substruc- 
ture, the fibroblasts and angioplasts of the latter growing up into 
and through the engrafted articular fragment, which is actually re- 
placed by the new connective tissue. The epithelium desquam- 
ates and only to a very slight extent is the graft the starting point 
for the formation of the new layer of skin. In reality the new 
graft is more like a piece of plaster, beneath which the formation 
of new elements from the adjacent structures may take place with 
facility (Durk). For success in such transplanations the size of 
the bit of tissue transplanted should be taken into consideration 
(even particles no larger than a pea may disintegrate in the central 
part because too much time is required to afford them proper nour- 
ishment), as well as the question whether the base of implantation 
affords thoroughly favorable conditions for nutrition. For example 



Transplantation of Skin and Glands. 253 

suppuration of the granulating surface interferes with proper at- 
tachment; and, as the function of the tissue depends greatly upon 
nervous influences growth of a transplanted fragment is sometimes 
prevented because of the lack of any natural nervous communica- 
tion. Again the portion to be transplanted ought to be kept as 
nearly as possible at its proper vital temperature (tissues have been 
successfully grafted, however, even after having been kept for 
from one to four days). 

While transplantation of bits of skin to new positions in the 
same individual, as to the ear in a rabbit, has met with fair suc- 
cess, attempts to graft from one individual to another have not 
been so successful ; and transplantation from the skin of an animal 
to man has failed in most instances. Efforts to transplant mucous 
membranes (that of the lip to the lid) and of keratous tissues (in 
the repair of corneal lesions), both in man and animals, have shown 
little uniformity. In transplanting cartilage, periosteal and bony tis- 
sue the graft as a rule persists for a long time and there may be 
noted a certain amount of increase of the cartilaginous and perios- 
teal cells. However, this is not active enough to permit it to be 
said that there is an active part taken by the graft in the repair of 
an existing lesion ; but rather that the fibroblasts, angioplasts and 
osteoplasts at the border of the lesion grow into the transplanted 
tissue and gradually take its place. Inasmuch as the transplantation 
of such material (small fragments or pieces of bone, the length of 
a finger, not necessarily fresh bone but with equally good results 
in the use of macerated or boiled bone or bone sterilized by heat) 
may materially aid and hasten the restoration of a given defect 
and the formation of a solidly ossified scar in it, the method has 
gained considerable importance in surgery. 

Experiments by Ribbert, Lengemann, Lubarch and Enderlen 
have proved that transplantation of small pieces of salivary glands, 
sebaceous glands, mammary tissue, thyroid gland, epididymis, ova- 
rian tissue, and liver tissue into the peritoneal cavity, anterior cham- 
ber of the eye, under the skin and within the lymph glands, is fol- 
lowed by more or less perfect adhesive growth and actual prolifera- 
tion of the glandular epithelium, with formation of new cellular 
extensions with development of gland spaces and persistence of the 
vitality of the transported tissue. Ribbert's graft of mammary 
gland tissue into the ear of a young guinea pig has special interest 
from the fact that when the animal bore young the transplanted 
gland began to secrete milk, 



254 Hypertrophy. 

Operative grafting of thyroid tissue in case of loss of this organ 
(as in goitre and operation for the removal of goitre), which is 
apt to cause serious and even fatal disease, may successfully com- 
pensate for the loss and is therefore of value from a therapeutic 
point of view.* 

Hypertrophy. Gigantism. 

By the term hypertrophy is meant the increase of the essential 
tissue of a part of the body, leading to enlargement of that part. 

Literally the term really means excess of nutrition ( virep and rpbcpos, 
nutrition), and from ancient times it was used to express increase in 
volume of tissues and organs when it was supposed that this depended 
upon an increase of the nutritive supply to the structure involved. Theo- 
retically and from the microscopic findings, two types of increase in 
volume may be conceived of : hypertrophy, in which the cellular elements 
are seen to be increased in size, and hyperplasia, where a numerical 
increase in the cells is the basis for the increase in the dimensions of 
the organ. [These are often spoken of as simple hypertrophy and numeri- 
cal hypertrophy.! 

Where the increase of tissue involves the functionating elements 
of an organ -or part, as the parenchyma of a gland or the muscle 
cells, it is spoken of as true hypertrophy; where, however, it con- 
sists in an increase of the supporting tissue or so-called interstitial 
substance alone (connective tissue, fat) it is a false hypertrophy. 

True hypertrophies occur because of increased demands upon 
the activities of an organ and because of its increased functional 
effort. Such examples are termed zvork hypertrophies. This is most 
frequently seen in muscles, a very common example being met in the 
increase in the skeletal muscles in gymnasts and the arm muscles of 
wood choppers and smiths. The increased cardiac force in those 
conditions of life in man and animals requiring continuously special 
power of the heart is an expression of an hypertrophy. The heart 
possesses in a marked degree the power of accommodation to in- 
creased demands upon its ability; its muscular substance in case 
of permanent increase of labor increases {accommodative hyper- 
trophy) up to a certain degree, determined largely by the relation 
to the body weight. According to the investigations of Bollinger 
and Parrot all animals which are required to exert much muscular 
energy because of their mode of life possess a heart heavier in 
proportion to the body weight than those animals which lead a 
sluggish life, as the dog in comparison with the hog, the deer in 

* In man thyroid preparations may he administered by the mouth. 



Compensatory Hypertrophy. 255 

comparison with the sheep. There are marked differences in this con- 
nection between those birds which are good fliers and the domes- 
tic fowls which stay more on the ground. (For details cf. Kitt, 
Pathol. Anatomie der Haustiere, II Bd. Chapter on the Heart. 
Verl. v. F. Enke, Stuttgart. II Aufl. 1901.) 

All diseases which increase the work of emptying the ventricles 
of the heart in the period of systole and which force the heart to 
continuously increased pumping effort, give rise to cardiac hyper- 
trophies, usually confined to one part of the organ according to the 
position of the opposition to the cardiac effort. Chronic valvular 
lesions, which interfere with the ready passage of the blood from the 
auricles into the ventricles, after a primary dilatation of the 
auricles cause hypertrophy of the auricular walls ; stenosis of the 
semilunar aortic valves causes hypertrophy of the left ventricle, 
stenosis of the pulmonary valve a hypertrophy of the right ventricle ; 
It is only by a heightened muscular force that the blood can be 
pressed forward in such conditions. If the cardiac hypertrophy 
is for a long time sufficient to accomplish the increased demands 
put upon its functional capability and thus prevents the serious 
results of the original disease or compensates for them, it is spoken 
of as a compensatory hypertrophy. 

Smooth muscles also become hypertrophied in case of increase 
of function, physiologically seen in the pregnant uterus, patholog- 
ically observed in marked degree in the intestinal wall where con- 
strictions in the lumen gradually develop, over which the chyme can 
be driven only by increased peristaltic force. The same thing is 
seen in case of the urinary bladder, resulting from narrowing of 
the neck of the viscus by prostatic enlargements or from involve- 
ment by urinary calculi, etc. ; and in the oesophagus in case of stric- 
tures. In all these cases there occurs both a multiplication and an 
increase in size of the muscle cells. 

In the glands of the body true hypertrophy and the necessity for 
increased effort become apparent where smaller or larger portions 
of the glandular parenchyma are destroyed, and are restored or re- 
placed by regeneration. In case this cannot fully obtain or does 
not occur at all, as in the liver tissue (after echinococcosis or chron- 
ic inflammations) the remaining portions of the organ become en- 
larged and the general volume of the liver may thus become greater 
than normal. Especially in case of bilateral organs where one lie- 
comes entirely incapable of function, the remaining one acts for 
the former, performs a correspondingly greater amount of work 
and hypertrophies (compensatory or vicarious hypertrophy), Where 



256 Hypertrophy. 

one kidney is removed in an experiment, in the course of but a few 
days thereafter the other begins to enlarge ; and it is not infrequent 
in slaughtered animals to find one kidney shrunken up and the other 
from one to two-thirds larger than the normal organ. The reason 
that the increase in volume does not reach double the normal is 
because all of the constituent elements do not hypertrophy in even 
proportion, the process involving particularly the secretory struc- 
tures, the glomeruli and the convoluted tubules, the epithelial cells 
of which enlarge and the coils become more intricately convoluted 
and therefore longer. Of course compensation for a functional dis- 
turbance of a gland by hypertrophy can result only in case there 
exist analogous tissue or a glandular rest* In this sense the 
lymph glands and the bone marrow, for example, might substitute 
for loss of the spleen, but not other kinds of glands. 

As a reason why glandular organs are forced to higher secretory 
activity in case of removal of a portion of their parenchyma, it may 
be assumed that following the ablation of the organic parenchyma 
there accumulate in the blood certain secretory stimulants, sub- 
stances which stimulate the gland cells. Whether these substances 
act directly on the protoplasm to stimulate it to productive activity, 
or whether the more active protoplasm takes up more nutritive ma- 
terial and is therefore enabled to throw off more products, is un- 
certain (Ribbert). The fact that muscles in a state of increased 
activity receive an augmented blood supply and in case of destruc- 
tive changes in an organ a similar hyperemia develops in its remain- 
ing tissue (due to the accumulation of materials no longer se- 
creted) suggests according to Ribbert an explanation for the oc- 
currence of hypertrophy, in that the persistent congestion distends 
the tissue, with the result of separating the individual cells from 
each other and thus gives origin to space for the increase of vol- 
ume and for the multiplication of cells. Not only is it to be sup- 
posed that free spaces exist between the cells but the protoplasm 
itself is substantially distended, its individual molecules separated 
from each other and this intracellular increase of space affords op- 
portunity for assumption of further elements which go to make 
up the protoplasm. Ribbert's theory of mechanical origin of tissue 
growth (cf. Regeneration) finds special applicability in the devel- 
opment of cardiac hypertrophy and the hypertrophy of muscular 

* [What is meant here is the persistence in undeveloped form of tissue 
capable of taking - up the morphology and function of the adult tissue which 
has been lost. Thus in the formation of an organ there may be embryonic 
elements in excess which are not employed in the formation or subsequent 
development of the organ, remaining as "rests" and undifferentiated. In 
case of loss of substance of the organ such representatives may perhaps develop 
to maturity and compensate for the destroyed portions.] 



Vacuum, Nervous, Inftanlmatory Hypertrophy. 257 

canals (vessels, intestine, urinary bladder or gullet), the cause in 
such instance always being a retention of the contents (increase 
of blood pressure, influence of calculi, obstruction to the movement 
of the chyme, etc.) causing primarily distension of the lumen of 
the part and stretching of the muscular wall. 

That a diminution of the factors of resistance of growth, of tissue 
resistance, favors hypertrophy {vacuum hypertrophy) is apparent 
in the liver in case of the existence of a diaphragmatic cleft ; the 
liver tissue invariably grows through such an opening, and, just. as 
a button goes through a button hole, forms a new liver lobe pro- 
truding into the thorax, the soft and elastic lung tissue offering but 
little opposition. Such intrathoracic hepatic lobes may sometimes 
be found larger than a fist (in sheep, cattle, swine). 

[The influence of nervous factors in some cases of hypertrophy 
can scarcely be doubted, although it is probable that for the most 
part such influence operates in ways conforming with the causes 
above mentioned. The ability to take up and assimilate nutrition 
is in relation with the trophic influence of the nervous system, and 
the condition of the vessels supplying nutrition has even more ap- 
parent dependence upon the nervous functions ; and so, too, the rela- 
tive tone or the opposite condition of relaxation of tissues is regu- 
lated by nervous factors. Variations in functional activity are often 
determined by nervous influences. Leaving aside such influences 
in which perhaps the nervous factor may determine hypertrophy 
by evident involvement of such influences as increase of blood sup- 
ply, the provision of mechanical relaxation of tissue or the stimu- 
lation of functional activity, there are more obscure examples (pos- 
sibly in the end explicable on the same grounds but not clearly 
showing such reasons for growth) which for the time are properly 
spoken of as nervous hypertrophies, as the enlargements in acro- 
megaly, for example, or the papillary enlargements of the skin in 
many warts.] 

Connective tissue hypertrophies are usually the result of chronic 
inflammation and chronic passive hyperemia, in cither of which 
there are features of tissue destruction and of tissue dilatation. 
Where the liver becomes enlarged and the scat of connective tissue 
induration from chronic inflammation there occurs primarily a de- 
struction of the liver cells and a coincident growth of the support- 
ing tissue; the termination of chronic lymphangitis of the cellular 
tissue of the foot in pachydermia (ruffle foot or bristle foot in the 
horse) may be explained by the idea thai at first the connective 
tissue spaces arc filled with lymph and exudate and later become OC" 



258 Inflammation. 

cupied by the proliferating- connective tissue. The formation of 
thick, keratous epidermal layers (keratoses) over callosities of the 
skin or inflamed and distended bursse is to be ascribed less to the 
direct influence of external pressure than to the pressure exerted 
from beneath by the hard and thickened cutis upon the epiderm 
(see also chapters on Regeneration and Inflammation). 

The occurrence of congenital hypertrophies of certain parts of the 
body may be due to a number of causes. Some examples are compen- 
satory hypertrophies, as when one kidney fails to develop the other grows 
to unusual size; others are due to chronic passive hyperemia in the. foetus 
caused by Constrictions by amniotic bands, as the hypertrophy of the pinna 
of the ear or of the penis, (cf. Chapter on Malformations, Spezielle 
pa the I. Ana to mi e der Hausticre, I Bd.). 

Inflammation. 

The term inflammation is applied to a condition of local irrita- 
tion of the tissues, the seat of some type of injury, in which there 
occur, as phenomena of reaction to the irritant, changes in the 
blood current and lymphatic How, exudation of the constituents of 
the blood, excessive secretion of glands, phagocytosis and prolifer- 
ation of the tissues. 

In dealing with inflammation we have to do with a series of 
processes which are nothing more than modifications and exaggera- 
tions of physiological procedures, in this case having for their ob- 
ject the defense of the organism against the harmful influences and 
the compensation for local disturbances of nutrition, and represent- 
ing abilities of the animal organism acquired through phylogenetic 
adaptation. (Leber, Metschnikoff, Diirk, Marchand, Schmauss and 
others). 

In the lowest unicellular organisms, as the amoebae, the phe- 
nomena of reaction to harmful influences are manifested by the 
properties of chemotaxis, phagocytosis and intracellular digestion. 
In the more highly organized forms of life, made up of differentiated 
cells, these defensive functions are assumed by certain groups of 
cells (Diirk) ; and in conformity with the complexity of structure 
and interdependence of tissues and organs and the variability of 
the injuries, these regulative and reparatory processes are made up 
of a number of separate phenomena which in their synchronous 
and consecutive operations are grouped together under the com- 
prehensive term, inflammation. 

In the class of harmful agents capable of inducing inflammation, 
the causes of inflammation or irritants, are included a great variety 



Causes of Inflammation. 259 

of foreign bodies, parasites, infectious substances, poisons and ther- 
mic influences which are spoken of as external causes. These 
do not act in reality as the immediate causes of the process but 
produce primarily some type or other of tissue change, as necroses, 
degenerations and injuries, and the inflammatory reaction is di- 
rectly due to an effort to compensate for these latter. 
[It is not the heat of the flame or the steel of the knife which 
actually causes the inflammation; these are probably at once with- 
drawn. They, however, alter the cells and tissues, and the inflam- 
matory reaction arises in reality to eliminate or isolate these altered 
structures and prevent their acting as irritants, and to make re- 
pairs for their loss.] One and the same influence, depending upon 
the intensity and duration of its operation, may be responsible for 
a number of types of tissue alteration; an irritant poison, an acid, 
may in different degrees of concentration, heat or cold, give rise 
perhaps to a simple hyperemia, to a superficial inflammation or to 
deep ecshars. Strictly speaking tissue necrosis is always produced, 
sometimes only superficially, affecting only epithelium and vascular 
endothelium and essentially microscopic in extent, at other times 
extending more deeply or involving decidedly larger areas and ap- 
preciable to the unaided eye. In the first instance reparation is ac- 
complished so quickly by phagocytosis and prompt regeneration that 
the full picture of inflammation is not developed, these two factors 
of inflammation alone occurring in the tissue ; in case of the de- 
struction of a larger amount of tissue, however, provided it is not 
fatal directly or from complicating infection and putrefaction, the 
inflammatory reaction with its entire group of phenomena results. 
A given infectious agent may in one case give rise to a rapid general 
infectious process with fatal termination or in another only to a 
typical local inflammation, as illustrated by the varying effects of 
bacillus anise pticus in the virulent or attenuated state and in the 
particular state of individual predisposition of the subject. In reality 
the animal body reacts to all physical and chemical injuries by the 
production of an inflammatory process, provided time be afforded ; 
that is, provided the injury does not involve a vital tissue or organ 
to such a degree as to immediately produce death from the func- 
tional disturbance. Where bacteria of extreme virulence, with 
hemolytic power and capable of rapid extension, invade the sys- 
tem, a bacteriaemia or toxic infection is said to exist ; in such cases 
there is not enough time permitted for compensation by an inflam- 
matory reaction for the disturbances occasioned. Were the micro- 
organisms of lower virulence, did they multiply more slowly at the 



260 Inflammation. 

focus of infection so that their toxines might be restrained or ren- 
dered in some measure inert, or if the animal body be especially 
well provided with bactericidal substances, the course of the disease 
would be protracted and there would be time for the tissue to set 
into activity some or all of the reactions belonging to the inflam- 
matory process. Inflammation may therefore, as the combined man- 
ifestation of a number of defensive efforts directed against harm- 
ful agencies, be looked upon as a curative process. When the forces 
brought into activity succeed in eliminating the source of harm the 
inflammation reaches in a relative measure its physiological termi- 
nation (Diirk) ; when, however, the reaction directed to the removal 
of harmful influences is not successful in eliminating them, when, 
perhaps, the latter multiply in the system, the organism perishes in 
spite of the inflammation, not necessarily because of the inflamma- 
tion but because of the infection or intoxication, or possibly actually 
because of the inflammatory reaction from the series of functional 
disturbances of the organs resulting from its onset. 

The Phenomena of Inflammation, — From the earliest centuries 
of our era, when the Roman physicians Celsus and Galen at- 
tempted to formulate a conception of inflammation, there have 
been recognized as cardinal symptoms of the process in the 
grossly visible parts of the living body: increased heat, redness, 
szvelling and increased sensitiveness of the inflamed part {color, 
rubor, tumor, dolor), to which may be added disturbance of 
function (functio Icrsa) as a fifth. These fundamental symptoms 
are, it is true, clearly appreciable in most acute, that is, rapidly 
developed, inflammations of the skin and mucous membranes ; 
but they are not invariably to be noted in the entire course of the 
process. The older the inflammation becomes, the more likely are 
these features to be lost one after another ; and a chronic inflamma- 
tion beginning gradually and continuing in low grade may not show 
any of them. Moreover the supposition that internal organs in in- 
flammation show the same intense redness, swelling, increase of 
temperature, and increased sensibility to pain, is only partly correct ; 
and here too the chronic inflammations are especially likely not to 
be characterized by such phenomena. 

In the effort to analyze the nature of inflammation from an 
anatomical standpoint modern studies have furnished definite ex- 
planations of the above mentioned symptoms of Galen and have 
given sufficient insight into the inflammatory process to afford a 
fairly precise knowledge of the character of the changes and the 
methods followed bv the tissues in their inflammatorv reactions to 



Phenomena of Inflammation. 



261 



irritants. Thanks to the studies of Virchow, Recklinghausen, 
Cohnheim, Ziegler, Marchand and others, the various steps which 
develop and take part in the process in inflamed tissues have come 
to be well understood. Only in connection with relatively unim- 
portant questions do there still exist differences of opinion and theo- 
retical discussions, involving for instance such points as whether 
the proliferation attending inflammation is produced by excess of 
nutrition or lack of tissue tension, whether it may be assumed or 
not that there is a functional stimulation to excite cell formation, or 




Fig. 47. 

Emigration of the leucocytes in frog's mesentery, six hours after exposure. The 
cells shaded with lines are the red corpuscles ; the stippled ones are the 
leucocytes; X 250. (After Terls.) 



whether certain granular changes of the cells should be spoken of as 
inflammatory or regarded as degenerative. 

The inflammatory process may be directly traced (Cohnheim's 
experiment*) under the microscope in transparent inflamed living 
tissue, as the mesentery of a frog or rabbit or in the expanded 
wing of a bat or the tongue of a frog drawn out from the mouth 
or in the web of a frog's foot, the inflammation being excited in 
such tissue by the application of a caustic or the production of a 
minute traumatic lesion. 

The first step of inflammation in a vascular tissue consists of 

♦For details cf. KKt, Bakterienkunde und pathol. mikroskopie fur TiGrSrete, 

IV Aufl. Wien, M. Perles Verlag, 1903. 



262 



Inflammation. 



distension of the blood vessels, hyperemia. In the exposed or irri- 
tated parts there may be first observed a dilatation of the arteries 
and later of the capillaries and veins. With this the blood current 
is first accelerated, but with the occurrence of dilatation of the veins 
of the tissue the circulation becomes slowed. Here or there it may 
stop for a variable period, and the corpuscles which previously 
were forced along in the central part of the stream become dis- 
tributed uniformly throughout the lumen of the vessel in the stag- 
nating blood. In addition the delicate capillaries, through which 
previously plasma mainly flowed with here and there a blood cell, 
are found engorged with blood corpuscles. With this slowing of 
the current the sluggishly moving white blood cells tend to collect 





j £ 



a 










IIPB 

Hfl 



Fig. 48. 



Various steps in the passage of a white blood corpuscle through the wall of a 
vessel. On the left of the short lines which represent the vessel walls, is 
supposed to be the intravascular blood; on the right the tissue; X 1,000. 
(After Thoma.) 



more and more on the inner surface of the vessel wall, giving rise 
to the so-called marginal deposition of the white corpuscles, and as 
additional ones are continually added from the blood the capillaries 
may, from their increasing accumulation, be found completely oc- 
cluded by leucocytes. There may next be observed a very charac- 
teristic feature, the exudation or emigration from the vessels of 
large numbers of the white corpuscles into the area of inflammation. 
These motile amoeboid cells, which were more or less flattened 
against the internal surface of the vessel, penetrate the capillary or 
venous walls by protruding a pseudopod-like process of their pro- 
toplasm through it (mainly at the cement lines between the endo- 
thelial cells) the rest of the protoplasm following in a distinctly 



Phenomena of Inflammation. 



263 



flowing manner until the whole cell is on the outside. In the living 
specimen all of the steps of the passage, so like a creeping move- 
ment, may be followed ; and in sections of an inflamed tissue cells may 
be found partly outside and partly within the vessels, fixed in their 
constricted condition and reminding one very much of the appear- 
ance of a wasp with its abdomen constricted from the thorax. Some- 
times these cells show a long stretched out protoplasmic process, 
swollen out into a button in case a part of the substance with the 
nucleus has moved forward. The leucocytes which have escaped 




Fig. 49. 

An inflammatory focus the seat of cellular infiltration in the tissue of the kidney. 

(Section of the kidney of a cat.) 

from the vessels continue their creeping movement and thus dis- 
tribute themselves in the spaces and interstices of the tissue of 
the inflammatory area between the connective tissue ceils and fibril- 
lary bundles, and wandering on between the epithelial cells to the 
free surface of the part. 

As new cells are constantly passing from the vessels the inflamed 
tissue becomes thickly studded with leucocytes, constituting a con- 
dition known as cellular infiltration. A number of authors believe 
that the leucocytes after their egress from the vessels multiply in 
the tissues by amitosis (direct division), and, too, that the lymphoid 



264 Inflammation. 

cells find their way into the part from the lymphatic foci scattered 
about in all organs. 

Along with the leucocytes the fluid blood plasma also escapes in 
greater or less amount from the distended vessels, by a process of 
leaking through the walls through the openings made by the leuco- 
cytes and directly through the endothelial cells which have from 
injury become more readily penetrable; or, as some maintain, the 
fluid is given off" to the tissues as a secretion of the endothelium. 
It is possible that red blood cells may also escape from the vessels, 
mixed with the fluid, being passively forced through any existing 
openings by the extra blood pressure. The transuded blood plasma 
with its cellular elements is known briefly as the exudate (from 
twsudare, to exude). 

The histological events just detailed place us in a position to 
understand why and how the phenomena spoken of as the cardinal 
symptoms of inflammation are produced. 

The redness (rubor) is the result of the hyperemia. In early 
stages of the process and in the peripheral zone of an inflammatory 
area, where the blood current is accelerated, this hyperemia has the 
characteristics of an arterial hyperemia, the vessels showing up 
conspicuously with a scarlet red color as if injected (injection red- 
ness, branched redness). The more pronounced the slowing of the 
current and the more the stagnating blood gives off its oxygen to the 
inflamed tissue the more the color approximates that of the venous 
blood, becoming darker and of a more violet hue and becoming 
more and more diffuse as the dilatation of all the capillaries de- 
velops. The heat (calor) depends upon the increased rapidity of 
flow and the volume of arterial blood ; the more rapid the current, 
the less opportunity being afforded for loss of heat and the more 
nearly the temperature of the inflamed part approximates the tem- 
perature of the blood itself. The heat of an inflamed area is only 
noticeable on the exterior of the body, in comparison with the parts 
whose temperature is unchanged, and is not above the temperature 
of the general blood. The internal organs do not become essentially 
warmer than the blood, special increase of temperature from meta- 
bolic changes not taking place in inflamed parts (Perls, Ribbert). 
[It is claimed by some, however, on the basis of experiments carried 
on it is true with difficulty and open therefore to a chance of error, 
that the blood coming from an inflamed part is of higher tempera- 
ture than that of the arterial blood going to such a part, and that 
increase of temperature is actually, therefore, produced in inflamma- 
tion presumably from an increased metabolism which obtains.] 



Signs of Inflammation. 265 

The swelling (tumor) of an inflamed tissue is easily comprehended. 
The exudate fills up the lymph spaces and stretches the structures 
apart ; the vessels are dilated, and the lymph is prevented from es- 
caping readily from the tissue because of loss of elasticity of the 
interstitial substance (Landerer). In consequence a turgescence, 
appreciable as an oedematous swelling in inflamed areas on the 
periphery of the body, occurs. In chronic inflammations the con- 
nective tissue proliferation gives to the organ or its connective 
tissue frame-work more or less increase of volume. The pain 
(dolor) is attributable to the pressure exerted by the exudate and 
swollen tissue upon the sensory nerve filaments or to direct irrita- 
tion of the latter. In addition this fault interferes with the trans- 
mission of nervous impulses, in consequence of which arises 
functional disturbance, in addition to the disturbance occasioned by 
the primary influence of the cause of the inflammation (death of 
tissue) and the simple mechanical disturbances produced by the 
collection of exudate in cavities (as the air spaces of the lung or 
the pleural cavities), the overgrowth of tissue, etc. 

As already stated, the processes involved in inflammation are 
nothing but modifications of physiological processes. Exudation of 
plasma and leucocytes and their movement through the tissues are 
continually going on under normal conditions ; the ordinary lymph 
formation is the result of a normal process which in inflammation 
is clearly only exaggerated. The reason for this heterometria, 
and more particularly for the circulatory disturbances, may be found 
in certain physical and chemical changes in the vessel wall. All 
inflammatory excitants apparently exert, directly or indirectly, 
chemical influences leading to changes of the endothelium of the 
vessels and thus making the vessel wall more permeable than nor- 
mally. It can be shown for example that the endothelial cells may 
be caused to shrink, contract into spherical form, and thus give rise 
to imperfections in their interstitial cement. These openings pro- 
duced pathologically facilitate the leakage of the plasma and the 
emigration of the leucocytes through the wall and make it possible 
for the red cells to undergo diapedesis. Changes in the tension 
of the vascular wall, relaxation of the arterial musculature, neces- 
sarily accompany lesions of the endothelial cells and the surrounding 
tissues, and this in turn occasions dilatation of the vessels. In every 
case, too, the nervous system, especially the network of vasodilators 
and vasoconstrictors distributed about the vessels, takes part in 
bringing about the vascular dilatation, these nerves bein^ affected, 
irritated or paralyzed, by the original cause of the inflammation. 



266 Inflammation. 

The acceleration of the blood current which is seen in the early 
stages depends on the passage of the blood from narrow into wider 
channels [an explanation sufficient for the short period required for 
the filling of the additional space afforded by the dilated lumen of 
the vessel, but not clearly satisfying for its continuation even for the 
time it does prevail before stasis sets in, and for its longer persist- 
ence at the periphery of the inflamed area] ; the slowing of 
the current upon the transudation of the plasma and the endothelial 
changes, both of which tend to cause a more concentrated condition 
of the blood. [Here, too, there should be considered the probability 
of relative inefficience in the outflow of the blood, loss of tone of 
the venous walls and loss of elasticity of the surrounding tissues, 
local compression of the walls of the capillaries and venules by exu- 
date and proliferating or swollen and degenerate cells, all of*which 
introduce elements of a relatively passive factor in the process for 
retardation of the escaping current.] The marginal deposition 
of the white corpuscles is explained by Hering and Schklarewski by 
the fact that when liquids containing light bodies in suspension are 
passed through tubes these bodies tend to move along the periphery 
as the rapidity of the current is slowed; they call attention to the 
lower specific gravity of the white in comparison with the red cells 
and their viscidity and tendency to adhere from their tactile irri- 
tability. The movement of these cells, physiologically determined 
everywhere by their tactile and chemotactic sensibility, is stimu- 
lated in inflamed tissues both by the causes of the inflammation 
and by the lesions occasioned by these causes. The studies of 
Pfeffer, Buchner and others have made us acquainted with a series 
of substances which possess marked power of attraction for leu- 
cocytes, especially certain proteins of the bacterial body ; and in the 
destruction of tissue induced as a primary effect of the untoward 
influences exerted by the causes of inflammation certain chemical 
substances, as the alkali albuminates, are set free which have a sim- 
ilar attractive influence upon the leucocytes. According to Thoma, 
even a variation in the amount of saline matter in a tissue will 
occasion a movement of the leucocytes. 

The spaces produced between the endothelial cells are appar- 
ently not primarily due to perforative efforts by the leucocytes, but 
result from distension of the vessel or from shrinkage of the endo- 
thelial cells ; and the leucocytes possessing tactile sensibility, closely 
adapting their substance to the surface and fitting into every varia- 
tion, extend their processes, tentatively and uncertainly, through 



Exudate and Proliferate. 267 

any existing openings. The presence of any substance with chemo- 
tactic power determines the direction taken in the further move- 
ments of these cells. 

The majority (about seventy per cent.) of the motile cells col- 
lectively spoken of as leucocytes, which are found in an inflam- 
matory focus, are characterized by the possession of multiple 
nuclei, or one polymorphous nucleus, and very fine granulations only 
seen in fresh specimens. These polymorphonuclear forms are re- 
garded as the characteristic white blood cells and arise from the 
bone marrow (where they are mononuclear, acquiring biscuit and 
clover leaf types of nuclei only in passing into the blood as the 
result of nuclear division or fragmentation). Besides these, which 
are described by Ehrlich as neutrophilic leucocytes, there are met 
in inflamed tissues forms containing coarser granules which, be- 
cause of the readiness of their granules to take up intensely the 
acid aniline dyes, like eosin, are known as eosinophile leucocytes ; 
and others with special tinctorial tendency of their coarse granules 
for the alkaline anilines (gentian violet), known as mast cells. 
Mononuclear (single nucleus) cells are also comparatively numer- 
ous in inflamed tissue, the nucleus round and rich in chromatin, 
and the cytoplasm showing as a very narrow margin about the 
small or large nucleus. These are regarded as lymphocytes, which 
have originated from the lymph glands or germinal lymphatic 
centres. As above mentioned, the great increase of these cells 
depends in part upon a chemical stimulation acting not only on the 
blood vessel walls but also upon the foci of lymphoid cells dis- 
tributed in all the tissues and causing enlargement of these lymph- 
cell forming centres ; and in the second place, as many of these 
cells have come from the marrow, it may be inferred that these 
chemical substances, which act locally in the inflammatory area as 
chemotactic agents and stimulants to proliferation, are also present 
in the circulating blood and with it pass into the bone marrow and 
there exert the same influence, that is, stimulate this tissue to the 
formation of leucocytes. Often in inflammation there is not only a 
swelling of the lymph follicles, but even a hyperplasia or meta- 
plasia (change of red marrow into lymphoid) of the bone marrow- 
referable to its exaggerated function. 

The causes of inflammation and the chemotactic substances set 
free in the affected tissue have, moreover, a stimulating influence 
upon the proliferation of the fixed cells. The endothelial cells of 
the blood vessels and lymphatics and the connective tissue cells 
take part in the proliferation in every inflammation, the beginning 



268 



Inflammation. 



of proliferation being indicated by the appearance of mitotic 
changes. After conclusion of mitosis the cellular division takes 
place, the protoplasm also increasing in volume. The young cells 
arising from this proliferation persist in part in the inflamed tissue, 
and after the formation of an' intercellular substance constitute an 
inflammatory embryonic tissue, -made, up of fibroblasts and angio- 
plasts, which serves the purpose of restoration of the original lesion 
(cf. Regeneration, p. 237). In part these cells disappear, and they 
may perhaps exhibit motile activity. A number of the proliferating 




Fig. 50. 
Inflammatory focus in kiduey of calf, showin: 



cellular infiltration. 



connective tissue cells and endothelial cells are sometimes changed 
by direct nuclear division into multi-nucleated giant cells. The forma- 
tion of these giant cells is by some supposed to be due to a chemo- 
tactic influence bringing a number of cells together and causing 
their fusion ; another suggestion is that the cause of the inflam- 
matory change has in some way disturbed the protoplasm of a cell 
so as to interfere with division of the cell substance, although 
nuclear division goes on. This type of cell is met especially in 
inflammation excited by foreign bodies, about which corpuscular 
elements the giant cells are found deposited in a manner explain- 



Demarcation and Phagocytosis. 



269 



ing how the inflammatory reaction is able to carry out its protec- 
tive purpose by removal or encapsulation of the harmful substances. 
Demarcation and Phagocytosis are two important functions of 
the cells coming into consideration in the inflammatory process. 
The motile cells of leucocytic and lymphoid types, distinguished 
generally for their phagocytic properties' even in normal circum- 
stances, are attracted by the metabolic products of an injured tis- 
sue or by the chemical influences of the inflammatory agents. They 
take up all the substances in a disintegrating tissue which are acces- 




Inflamm 



Pig. 51. 
atory scar in the kidney of a hog. 



sible and with which they can deal, as albuminous granules, blood 
remnants, pigmentary granules and fat globules, and, indeed, all 
sorts of minute particulate elements, as vegetable and animal micro- 
organisms ; carrying these objects off or destroying and rendering 
them inert by the influence of the digestive power of their proto- 
plasm. However, this power of phagocytosis also resides in the 
fixed cells. In the chemotactic accumulation of the cells, which 
takes place around foreign bodies or necrosed tissue, the leucocy- 
tes, fibroblasts and angioplasts and giant cells form a protective 
wall which cither permanently imprisons the foreign body or from, 



270 Inflammation. 

which fresh cells constantly move into the dead structure, grow 
all through it and break it down, bearing away particles of the 
disintegrated material or any minute foreign elements (bacteria, 
etc.), and in this way gradually removing the agents producing the 
inflammation. 

These features have ' been studied experimentally in a variety 
of ways. They may be easily observed by injecting into a tissue 
an emulsion containing fine particles of carmine. An inflamma- 
tion is determined in the course of which the leucocytes and fibro- 
blasts become loaded with pigment granules, and giant cells are 
formed which also englobe the pigment particles. Some of the 
carmine is carried out of the area by the motile cells ; when larger 
amounts have been introduced the parts which cannot be carried 
away are encapsulated by the connective tissue cells and the cica- 
tricial tissue arising from the latter. When porous foreign bodies 
like bits of sponge or elder pith are introduced aseptically into the 
subcutaneous tissue or into the peritoneum, at first the exuding 
plasma and a large number of leucocytes occupy the spaces in the 
substance, but later the connective tissue corpuscles and vascular 
buds penetrate into them and take up all the available space (this 
reactive proliferation is seen as early as the second day). 

After transformation into scar tissue (v. p. 241) the connective 
tissue is found surrounding and filling all the spaces of the foreign 
substance and isolating it from the rest of the organism (Ribbert). 
Solid foreign material like silk thread, cat gut, silver wire, intro- 
duced aseptically as sutures by surgeons, or bullets, needles, bits of 
glass, wood splinters, or hairs which have gotten into' wounds, pro- 
vided they have no bacteria upon them and are truly aseptic for- 
eign bodies in the tissue, are always surrounded by a wall of leu- 
cocytes and proliferating connective tissue and thus encapsulated. 

The inflammatory reaction about a foreign body always depends 
upon the soluble chemotactic substances which arise from the mate- 
rial. About some bodies which give rise to but little substance of 
this sort (aseptic cat-gut, silver wire) it may be very unimportant; 
inflammation ceases entirely after these substances are completely 
extracted from the foreign body, that is when it* can no longer 
give off soluble chemotactic material. The functional activity and 
the movement of the cells mentioned toward the foreign matter can 
be beautifully demonstrated, as pointed out by Ribbert, by inject- 
ing liquefied agar or a blue-stained mass of gelatin into the sub- 
cutaneous tissue or anterior chamber of the eye. Soon after the 
jelly has hardened in the body it is surrounded by leucocytes and 



Inflammation in Non-Vascular Parts. 271 

fibroblasts which approach; these cells push forward and into the 
jelly like a phalanx of soldiery, break it down and gradually carry 
it entirely away; and the local inflammatory condition disappears 
with the removal of the foreign matter, the leucocytes and other 
cells being able to return whence they came, or some perhaps dying 
and undergoing disintegration. 

Hemorrhagic effusions, blood clots, masses of fibrin, coagu- 
lated or completely necrosed tissue and loose bits of bone are all in 
the same way objects for phagocytic activity of the cells, making 
their appearance in the tissue reactions in inflammation. All dead 
tissue, in fact, is the same thing as a foreign body in relation to 
the functionating living tissue adjacent to it; it is a source of 
chemotactic substances and acts as an excitant of inflammation. So, 
too, just as non- vital foreign bodies, the living organisms which 
enter the body from the exterior, the animal parasites and all 
microbes, are to be looked upon as irritants and as causative of 
inflammation to a greater or less degree, according to the chemo- 
tactic substances which they contain. 

Inflammation in non-vascular parts of the body, of which there 
are two which require special mention, the cornea and the cardiac 
valves (cartilage and the calcified bone substance, which are also 
avascular, have no marked inflammatory reactive power and are 
subject merely to retrograde metamorphoses), presents practically 
the same features as in the vascular tissues, save that emigration 
and exudation of course cannot take place where there are no ves- 
sels, but do occur from vessels at a distance. Numerous investi- 
gators, particularly His and Virchow, and besides these Cohnheim, 
Fuchs, Eberth, Ranvier, Guterbock, Ribbert and Marchand, have 
engaged in studies in connection with the process in question, and 
have thereby materially added to our appreciation of the nature of 
inflammation. Where the cornea has been injured by some trau- 
matic lesion, by a foreign body, or some type of infection, leuco- 
cytes actively penetrate to the focus from the blood vessels which 
encircle the margin of the cornea in the conjunctiva. Although 
these vessels are situated some distance from the focus of injury 
there are to be noted in them the same dilatation, slowing of the 
current and emigration as if they were immediately in the injured 
area. It is probable that these vessels are influenced by reflex ner- 
vous action, and it cannot be doubted that the injured corneal tissue 
exerts a strong chemical attraction for the leucocytes by means of 
substances dissolved in the corneal lymph and reaching the corneal 
margin in the latter or exerting a far-reaching influence from 



272 Inflammation. 

within the corneal mass. The leucocytes which escape from the 
blood vessels at the corneal border find their way along the spaces 
of the corneal tissue to the point of injury and there collect about 
it. This can be observed in the frog's cornea which has been 
touched with a corrosive, if the animal be killed a day or two later 
and the excised cornea spread out on a glass slide, as the leucocytes 
of this cold-blooded animal retain their motility for a considerable 
time. The wandering cells are found elongated and conforming 
in shape to the narrow tissue spaces, their presence giving the cor- 
nea a milky cloudiness. At the same time the corneal cells are 
found proliferating ; they undergo division and become slightly 
motile in response to the chemotactic agent connected with the 
inflammation. If the inflammation continue for a comparatively 
long time, eventually the marginal vessels begin to send vascular 
buds into the cornea ; these may penetrate so far that the cornea 
becomes covered or completely penetrated by a network of vessels, 
a pannus ( r? ir-fivq. a cloth). This proliferation is also, according 
to Ribbert, probably due to a chemotactic stimulus affecting the 
endothelial cells. The opacity which involves the cornea in the 
course of the process mentioned may entirely disappear with the 
completion of repair ; the transparency returns because the cells 
creep back and the fluid washes out the products of disintegration 
and the capillaries undergo regressive changes. In other cases a 
whitish scar remains as a remnant of the proliferated tissue. 

Inflammation of the cardiac valves, according to Ribbert, is not 
attended by penetration of leucocytes into the tissue at all ; aside 
from the formation of adhesive clots, which develop upon the 
roughened (from endothelial lesion) leaflet, the only evidence of 
reaction consists in a multiplication of the fixed cells of the endo- 
cardium and, in case the process continue for a time, of the pene- 
tration of the capillary vessels from the base of the valve into its 
substance. 

Anatomical Types of Inflammation and Exudation. — Exudation 
of blood plasma, emigration of leucocytes and sometimes diapedesis 
of red cells occur in varying degree, depending upon the causes of 
the inflammation, its duration and local conditions ; and give rise 
to special appearances which form the basis for differentiating a 
number of forms of inflammation and exudate. 

The volume of exudate varies within wide limits ; it may be so 
small that the inflammatory focus can be found practically only 
with the aid of the microscope, or there may be such a quantity of 
fluid that many liters may be removed (from the larger cavities of 



Serous and Fibrinous Inflammations. 273 

the body). The exudate may exist in the lymph spaces of the tissues, 
filling them completely (infiltration), or may escape to the surfaces, 
where it forms a deposit upon the latter; it may collect in the body 
cavities or may find free exit from the body. Even in normal con- 
ditions leucocytes find their way between epithelial cells, and when 
the epithelial tissues are loosened in inflammation or actually des- 
quamated the exudate is given easy access to the free surface. The 
qualitative composition of the exudate is by no means uniform ; 
sometimes the major portion is plasma and cells are but scantily 
met in it, sometimes the reverse is true. In addition admixtures of 
the secretions of organs may be found present, or products of tis- 
sue disintegration or changes due to coagulation, putrefaction or 
inspissation, all of which serve to give a very variable character to 
the exudation. 

The terms serous exudate and serous inflammation are employed 
in connection with an aqueous product of inflammatory extravasa- 
tion ; the fluid is rich in albumen, like the serum of the blood, lim- 
pid or slightly clouded, of a yellow wine tint, or sometimes red 
from the presence of erythrocytes. When it soaks through a tissue 
and gives it a juicy gelatinous appearance the structure is said to be 
the seat of inflammatory oedema; collecting in the sacs of joints, 
tendon sheaths and the serous cavities the expression inflammatory 
dropsy is applied. In' the skin surfaces, which are covered with 
squamous epithelium, the upper layers of which are but slightly 
permeable for fluids, it may collect in the more easily penetrated 
deeper layers of the rete Malpighii and raise up the superior strata 
to the formation of blisters. In mucous membranes the fluid passes 
through the epithelial layer and mingles with the physiological secre- 
tion and the desquamated cells of the membrane, escaping with 
these ; in this case the term catarrhal exudate {Karaptu, to flow 
away) is employed. Such catarrhal exudate may be very thin and 
water like, or may be viscid. The irritation of the inflammatory 
condition invariably induces an increase of secretion (increased flow 
of tears, increased secretion of nasal mucus). 

It is said to be a fibrinous exudate in case the exuded fluid under- 
goes coagulation by precipitation of fibrin. This form is met par- 
ticularly on the free surfaces of serous membranes and mucous 
membranes, within joints and in the lung, and to a less degree in 
the meshes of the tissue. Coagulation occurs in case the fibrin 
forming substance, which is always abundantly present in every 
exudate, conies in contact with fibrin ferment, the latter being sup- 
plied by necrosing cells, especially leucocytes and endothelial cells. 



274 



Inflammation. 



The fibrinous exudate may form delicate or thick, more or less ad- 
herent, grayish white to yellow deposits or flocculent precipitates 
of a semi-transparent, elastic type. On the surfaces of serous mem- 
branes it may be observed as a frost-like deposit of thick patches 
of coagulated substance which can be torn off in shreds, look some- 
thing like omelet and perhaps cover considerable areas of the 
serous surface {false membrane). The viscidity of the exudate is 
responsible for the fact that on opposed surfaces which move over 




Fig. 52. 
Fibrinous exudate on surface of heart of cow (traumatic pericarditis). 

each other (pleura, diaphragm, peritoneum) the layers of exudate 
in rubbing upon each other leave the fibrinous material stretched 
and dragged into a reticular, villous appearance, reminding one of 
butter on two pieces of bread which have been pressed together 
and then pulled apart, or of the ridged appearance of tripe {dry or 
fibrinous exudation). In other instances the coagula of fibrin are 
so large as to appear as elastic rind-like layers, thick as one's hand, 
riddled with tiny holes which contain serum ; or the serous exudate 



Fibrinous Inflammations. 275 

may predominate and flakes of fibrin be found floating in it, in a 
state of fine division (sero-fibrinous exudation) . On the mucous 
membranes also the fibrin may be encountered as membranous lay- 
ers, which may be pulled off in sticky shreds, and which sometimes 
form distinct casts of the canal; these are spoken of usually as 
croupous exudates (according to Roth the word croupous has a 
Scottish origin). Croupous membranes may be tough or soft and 
grumous, depending upon the proportionate number of cells present 




-^$P<^tppS;fe>& 









^0k 











Fig. 53. 

Enteritis membranacea of cat (section). To the left the pseurlomembrane cover- 
ing the intestinal villi, which are the seat of cellular infiltration and des- 
quamation; to the right the muscular layers and the serosa with its adipose 
tissue. 

and the existence of some degree of degeneration ; they vary from 
one-half to ten millimeters in thickness ; when separated in the form 
of tubes they are full of the contents of the mucous canal, as the 
intestine, in which they develop ; in other instances, as in the lungs, 
they form solid coagula. Under the microscope, at the beginning 
of fibrin separation the fibrin threads can often be seen arranged in 
a stellate, tuft-like manner about the cells which give origin to the 
fibrin ferment (Hauser) ; sometimes the fibrillar material is depos- 
ited in parallel layers or is formed in a reticulum, the meshes of 



2j6 



Inflammation. 



which are occupied by leucocytes, desquamated epithelium and 
serum. By the cohesion of the fibrin, originally separated in the 
form of fine fibrils, thick homogeneous trabecula are sometimes pro- 
duced (hyaline fibrin). 

Fibrin may be well demonstrated in 
microscopic sections by Weigert's double 
staining method, the fibrin taking an in- 
tense blue tint, and the rest of the tissue 
a red contrast color. 

Inflammations of mucous mem- 
branes, in which in addition to the 
formation of a fibrinous exudate there 
takes place a coagulation necrosis of 
the tissue of the mucous membrane, 
are spoken of as diphtheritic inflam- 
mations ( 5«petpa, membrane). The 
coagulation-necrotic mass is here 
seen as a grayish-yellow to straw- 
colored or dirty gray, soft and pulta- 
ceous or drier, very opaque and usu- 
ally fragmented material, which 
stands out sharply from the slightly 
transparent normal tissues as a 
thicker, somewhat swollen, promi- 
nent part. Here the deeper parts of 
the mucous membrane are permeated 
with the exudate, and the substance 
cannot be as readily separated from 
the underlying tissue as the ordinary 
croupous . exudate, the mucous friem- 
brane being torn when attempts are 
made to scrape it away. 

This combined inflammation and 
necrosis in its typical form is met in 
the digestive tract of swine affected 
with swine plague, and is often seen 
in calves in the pharynx and larynx following traumatic 
infectious influences, in birds in the mucous membranes of 
the head, and in horses in the larynx and trachea after drenching. 
There are a number of microorganisms (bacillus necrophorus, 
suipestifer, streptococci and others) which are capable of inducing 
coagulation necrosis of tissues and giving rise to the anatomical 
picture of a diphtheroid inflammation. 




Fig. 54. 

Croupous membrane in trachea 
(opened) of cow. 



Suppurative Inflammation. 2JJ 

(In man the name diphtheria is applied to a specific infectious disease 
caused by bacillus diphtheria, usually accompanied by deeply penetrating 
fibrinous inflammation of the pharyngeal mucous membrane. Anatomically 
similar conditions, due, however, to other causative agents, are spoken of 
as diphtheroid, to distinguish them from true diphtheria. This name 
diphtheria has not been happily chosen, however, as it really means inflam- 
mation of the membrane.) 

Suppurative Inflammation with its product pus (Latin, pus; 
Greek, rb irvov) is characterized by the liquefaction of the exudate 
and inflamed tissue (purulent softening) and by the important pres- 
ence in the exudate of fatty degenerating leucocytes which have lost 
their power of movement; in addition it is always the result of in- 
fection with microorganisms known collectively as the pyogenic 
bacteria (pus bacteria). There are a number of these microorgan- 
isms occurring free in nature, mainly belonging to the groups of 
staphylococci, streptococci and colon bacilli, which are liable to gain 
access to the tissues through traumatic lesions or which may even 
penetrate from the unbroken surface through the pores of the skin 



Fig. 55. 

Sinai] intestine (laid open) of hog showing diphtheritic inflammation in swine 

plague. 

or through lymph follicles. In addition to these specific pyogenic 
bacteria, whose most important influence is the production of pus, 
there are many other microphytes which are also capable of induc- 
ing suppuration, but which, because of special peculiarities of their 
toxic properties and the peculiarities of the diseases which they 
cause, receive special names, as the glanders bacillus, bacterium of 
chicken cholera, and actinomyces. Wherever suppuration occurs in 
a part an infection is to be suspected. This statement, first empha- 
sized by Lister and Hunter, and of the utmost importance in sur- 
gery, is not impaired by the fact that suppuration may be artificially 
produced in experimental manner without the aid of bacteria by 
means of aseptic chemicals as by subcutaneous injection of turpen- 
tine, croton oil, chloride of zinc or corrosive sublimate, under con- 
ditions which thoroughly exclude the possibility of infection. Such 
an aseptic suppuration occurs under natural conditions only in the 
rarest instances, and differs from the ordinary bacterial suppuration 



278 Inflammation. 

in its definite local limitation. Bacterial suppuration is progressive 
and is accompanied by a more or less severe febrile general reac- 
tion on the part of the subject. 

As it is equally possible to obtain a suppurative inflammation by 
means of sterile germ-free cultures of the pyogenic organisms or 
nitrates which contain only the metabolic products of the bacteria, 
it may be accepted that the pyogenic action of bacteria is another 
instance of chemical activity; an important factor, however, being 
the presence of these living organisms which multiply in the tissue. 
The conception of suppuration is therefore an serological one. The 
pyogenic organisms exert, apparently by means of their toxines 
which are diffused through the tissues, an extremely strong chemo- 
tactic stimulus upon the leucocytes and in this way induce a greatly 
increased emigration of these cells ; at the same time they have an 
important harmful influence upon the walls of the vessels and nerves, 
thus causing hyperemia and voluminous exudation, and produce 
materials which destroy and liquefy the tissues which they involve. 
Their power of liquefying animal albumen and gelatine may be rec- 
ognized in cultures of the organism grown in solid gelatine and 
solidified blood serum, these media being dissolved by peptonizing 
enzymes produced by the bacteria. Leber has pointed out, however, 
that liquefaction of the tissues is to some degree due to the influence 
of the emigrated leucocytes or a proteolytic enzyme given off by 
these cells ; for example, the liquefaction attending streptococcus in- 
fections must of necessity be caused by the cells, as these organisms 
do not liquefy the above mentioned nutrient media. 

Pus appears as a dull yellow, yellowish-green or grayish-white 
fluid, opaque and creamy, thin and milky or more thick like egg- 
albumen, according to the amount of plasma it contains, becoming 
reddish-gray or of a cafe-au-lait color in case of greater diapedesis 
of the red corpuscles. It is often mixed with fibrin in the form of 
small flakes or shreds, which gives the pus a doughy consistence 
{Hbrino-purulent exudate) and fills the tissues with a fine reticulated 
structure. 

Under the microscope pus shows great numbers of leucocytes, 
mainly of polynuclear or polymorphonuclear type, showing instead 
of one single round nucleus a number of nodular (biscuit and 
clover-leaf forms) and fragmented portions of nuclear substance. 
The continually penetrating leucocytes, among which are also mono- 
nuclear examples, are similar to those found in the blood. In most 
of them, and eventually in all, necrosis is recognizable because of 
nuclear fragmentation and more certainly by the presence of fatty 



Pits. 



279 



degeneration. The cells become highly granular, the protoplasm 
full of fat vacuoles, and irregular, and finally the cells become 
nothing more than a bunch of fat globules held together by 
the protoplasmic remains (fatty granular cells) or falling 
apart into fatty detritus. The leucocytes, now known as pus 
corpuscles, and incapable of further motility, are suspended in 
the fluid portion of the exuded plasma, here known as the 




Fig. 56. 
Pus from cow; unstained microscopic preparation of pus cells (highly magnified). 

pus serum [liquor puris], or are deposited in the meshes of the 
tissue. The cells of the tissue in which the suppuration has taken 
place are also the seat of marked fatty degeneration ; the connective 
tissue corpuscles and cells of the vessel walls often exhibit phagocytic 
appearances and are found with leucocytes englobed within their 
substance; and in, chronic inflammations always multiply, thus lead- 
ing to restoration of the lesion or its encapsulation. The pyogenic 



28o 



Inflammation. 



bacteria arc usually found in comparatively large numbers in the pus 
serum and sometimes the leucocytes are loaded with them. Accord- 
ing to the manner of commencement of the process a single variety 
may be found present as a perfectly pure culture, or there may be a 
number of forms associated together. As occasionally occurs in 
chronic cases, if no microorganisms can be discovered it may be 
assumed that the bacteria have gradually died in the pus and have 
undergone disintegration. If the suppuration occurs on the surface 
of a mucous membrane it is spoken of as a purulent catarrh, 




Fig. 57. 
Film preparation of pus cells, stained with fuchsin (highly magnified). 

pyorrhoea, or blenorrhcea ((3\epva, mucus; pea, to flow). In such 
cases the blood vessels of the mucosa and submucosa are found 
dilated, containing large numbers of leucocytes, and the latter cells 
profusely accumulated in the meshes of the whole mucous mem- 
brane and penetrating between the epithelial cells of the surface. 
The epithelium is loosened, often hanging loosely in shreds. In 
addition the formation of mucus is increased, and many epithelial 
cells may be found transformed into goblet cells. 

This viscid secretion, mixed with desquamated epithelium and 



Suppurative Inflammation. 



281 



emigrated leucocytes, constitutes the fluid catarrhal secretion. On 
serous surfaces exudation is also attended with desquamation of 
the endothelial cells, and the exudate accumulates in the cavity 
lined by the serous membrane. A collection of pus in one of the 
large structural cavities of the body (pleura, joint, antrum of High- 
more) is called an empyema (tfi-irveiv, to contain pus). When pus 
is distributed all through the spaces and meshes of tissue, it gives 
the latter a dull yellowish-white or gray color and can be expressed 
from it in drops by squeezing between the fingers (purulent iniil- 



a , 




- ->* 



Fig. 58. 

Purulent nephritis of mixed type, from calf: a, microscopic abscess: b, embolus: c, 
normal urinary tubules ; d, urinary tubules devoid of their epithelium, con- 
taining coagulated material. 



tration). Where it collects in larger lymph spaces or occurs in cav- 
ities formed by local liquefaction of the tissue, it constitutes an 
abscess (pus sac), that is, a hollow space filled with pus; from pro- 
gressive tissue destruction and continued entrance of leucocytes 
such an abscess may attain considerable dimensions (size of a fist 
or head). A circumscribed collection of pus in the stratum Mal- 
pighii, elevating the keratous epiderm over it, constitutes a 
pustule (pus vesicle). When a purulent infiltration extends over a 
large area of subcutaneous, submucous or other loose cellular tis- 



282 



Inflammation. 



sue, with production of spaces filled with pus and confluence of 
abscesses the condition is called a phlegmon. Where the tissue soft- 
ening or the gravitation of the pus into dependent positions allows 
the exudate to escape the abscess is said to break or perforate ; and 
if in such instances there are formed narrow canals lined with pus 
and reaching to the surface these are called fistula. A loss of sub- 
stance upon the external surface or in mucous membranes caused 
by suppurative destruction of the tissue is known as an ulcer, the 
process as ulceration. 

In chronic suppurations in the zone between the dead tissue 
breaking down into pus and the normal tissues, there occurs a fibro- 




Fig. 59. 

Section through a calf's kidney riddled with embolic abscesses ; calyces and pelvis 

full of purulent masses. 

angioplastic proliferation, as a bacony, light gray, firm tissue. The 
suppurating focus is encapsulated by this demarcating grozvth, that 
is, it is enclosed in an abscess wall, which on its inner surface 
usually has a grimy, grayish-yellow or slate-gray color. As long as 
virulent pyogenic bacteria exist in the cavity this abscess membrane 
continues to give rise to more pus' [only in the sense that the exuda- 
tive processes which underlie the appearance of the leucocytes and 
fluid are largely going on within it, and not in the sense of a secre- 
tion as formerly believed] in the focus, for which reason it 
is sometimes known also as a pyogenic membrane. The involuntary 
muscle and elastic tissue of arteries exhibit marked resistance to 
purulent softening; in suppurative cavities, as of the lungs or udder 
or of a muscular tissue, vessels are often found as bridge-like 



Hemorrhagic, Gangrenous Inflammations. 283 

bands running across the space, perhaps as thick as a lead pencil, 
their walls not destroyed by the suppurative process but hardened 
by cicatricial proliferation and resisting destruction. 

The vascular connective tissue which develops upon exposed 
suppurating surfaces (ulcers, surfaces of wounds) presents a red- 
dish-gray color and a granular or finely nodular, uneven appearance 
{granulation tissue) ; purulent exudate arises from this also so long 
as the microorganismal cause of inflammation continues active. This 
tissue serves to restore the tissue loss, filling out the cavity into scar 
tissue (cf. Regeneration). 

With multiplication of the pyogenic organisms in the affected 
tissue not only does the local suppurative inflammation become cor- 
respondingly prolonged, but there arises the probability of its exten- 
sion. The bacteria advancing along the lymph spaces give rise 
to fresh inflammatory reaction in a constantly expanding area. The 
fact that the leucocytes have wandered into the suppurating area, 
may take up some of the bacteria and carry them some distance 
away, until stopped by the occurrence of paralysis and death 
and their transporting function thus ended, gives an excellent 
opportunity for the entrance of pus-producing germs into the lymph 
channels, lymph nodes and even the blood. Malignant and actively 
multiplying organisms, over which the bactericidal forces of the 
blood have no influence and the phagocytic cells no power, 
are thus likely to set up new foci of suppuration, so-called metas- 
tatic suppuration, in the lymph glands and any other places into 
which they have been carried as emboli. 

We speak of hemorrhagic inflammation, where the exudate 
contains a notable admixture of red blood cells, and is consequently 
of a reddish, grayish-red to dark red, chocolate or cafe-au-lait ap- 
pearance. Serous as well as fibrinous and purulent exudates may 
assume this character, which may be regarded as indicative of 
some especially severe disturbance of the vessel walls, which in 
turn has occasioned marked slowing of the blood current in the 
inflamed part, diapedesis of the erythrocytes or actual rupture of 
the vessels, and is therefore accompanied by stasis and haemorrhage. 

Putrefaction of the exudate and of the inflamed tissue (ichorous, 
gangrenous or putrid inflammation) is necessarily the result of the 
invasion of putrefying bacteria into the necrotic tissue and the 
masses of blood and exudate, dead material like the tissue itself. This 
combination of inflammation and moist gangrene, or, rather, the 
secondary changes produced by gangrene, breaks down the tissue 
or exudate into a dirty, grayish-green or dark green, malodorous 



284 * Inflammation. 

material and indicates an unfavorable prognosis for the inflamma- 
tion because of the almost unavoidable absorbtion of toxic matter 
into the fluids of the body. 

All chronic inflammations, whatever the character of the exu- 
date, result in the production of vascular connective tissue; the 
existence of a bacony, indurated, semitransparent or opaque milky 
tissue in or about an inflammatory area is a distinct evidence of 
its chronicity. « This is said to be a productive inflammation. What 
factors are responsible for this tissue formation cannot be definitely 
determined. It may be assumed that the same chemotactic in- 
fluences, which are at the bottom of the escape of the leucocytes 
from the vessels, stimulate the physiological formative energy of 
the cells, in other words exert a demand for growth. The young 
cells derived from these fixed cells are capable of some degree of 
motility and indeed do move ; and the growing connective tissue cells 
and endothelial cells are forced to take the direction in which 
chemotactic and nutritive materials are located. The primary exu- 
date, especially fibrin, possesses this power of attraction, the fibro- 
blasts beneath a fibrinous covering being found actively proliferat- 
ing and pushing into the fibrin. It is possible that the infiltration 
of a tissue with exudate directly occasions an excessive nutrition 
of the cells, enabling them to form more protoplasm and then di- 
vide ; and again the formation of spaces and the loss of substance 
of the tissues should be considered, these factors favoring the de- 
velopment of inflammation, and having a tendency to increase physi- 
ological regeneration by release. of tissue tension. The area of the 
proliferation depends upon the extent and duration of the inflam- 
mation. As already stated, the embryonic tissue appears in the form 
of granulations upon free surfaces (wounds, ulcers, fistulous pas- 
sages, serous membranes). With a reddish-gray or fleshy red color, 
it presents a granular, uneven, undulating surface, from which in 
aseptic inflammation is given off a serous, reddish, viscid exudate, 
or when bacteria are present a purulent fluid. The granular appear- 
ance which gives to the tissue its name (granulum, a small grain) 
is due to the projection of the outward growing capillaries w T hich 
extend out in loops and intertwine about the arteries like the top 
branches of the trees in a leafy wood. The precise tint of the 
granulation tissue, at times more deeply red or again more grayish 
red, depends upon the relative engorgement of the capillaries or 
the predominance of the gray color of the cells lying between the 
vessels. These intercapillary cells are leucocytes and fibroblasts, 
usually spindle shaped. On serous surfaces granulation tissue is apt 



Chronic Inflammation. 285 

to present a villous appearance, with finger-like, reddish and later 
whitish processes (filaments) ; growing in a fluid exudate this new 
tissue is found floating and waving back and forth with the move- 
ments of the viscera. When there is motionless contact with an 
opposed and similarly inflamed surface, the two surfaces become 
adherent, at first by the embryonic tissue, but later by capillary 
anastomoses and the thorough interlacing of the developing tissue. 
Thus adhesive inflammation, the formation of adhesive bands, often 
in the form of broad connective tissue cords, results. When 




-•'// '.*?? -'s; ''?.>?>* 









Fig. 60. 
Granulation tissue from skin of horse. 

the embryonic tissue develops beneath a serous surface it may give 
rise to broad flat pale areas of thickening, the so-called milk patches. 
About abscesses it forms abscess walls ; along fasciae or extending 
along other connective tissue structures (submucous, subcutaneous 
tissue or about fistulous passages) it forms extensive indurated 
layers. When the process involves the connective tissue structures 
of an organ diffusely, as between the columns of liver cells or in 
the kidney, this interstitial inflammation occasions a widespread 
firm induration of the organ (indurative inflammation). The in- 
flammatory embryonic tissue gradually becomes pale and linn and 



286 Inflammation. 

tough, the young fibroblastic elements like the cells from which 
they were derived giving rise to a fibrillar intercellular substance 
(cf. Regeneration). The bundles of fibrils continually growing 
thicker add firmness to the tissue, and with the cessation of inflam- 
mation the young tissue shrinks gradually to smaller bulk. By 
such changes it is transformed into scar tissue, here producing the 
depressed scars of surfaces, there constricting the lumen of tubes 
(stenosis, atresia), or again permanently and securely enclosing 
necrotic tissue or foreign bodies (encapsulation). Productive in- 
flammation usually stops when the lesion which caused the inflam- 
mation has been finally dealt with, that is after elimination or en- 
capsulation of the foreign body, necrotic tissue or other substance 
which originated the inflammatory process. Where, however, the 
irritation continues and final cicatrization is delayed the prolifera- 
tive changes sometimes take on an exuberant character. This may 
be particularly well seen in superficial granulations, which may 
grow up out of the lesion as projecting tumor-like masses (wild 
flesh, caro luxurians, granuloma) [proud flesh] perhaps as large 
as a human head. Indeed, interstitial proliferation of fibroblasts 
proceeding uninterruptedly for a long time may produce a mass of 
young inflammatory tissue far in excess of the original tissue it 
replaced and producing huge connective tissue enlargements (iibro- 
matous inflammation, fibrous hypertrophy) . On mucous membranes 
as that of the gall bladder, such proliferations meet but little re- 
sistance from the fluid in the cavity and often give rise to villous 
enlargements (polyps). 

Specific Inflammations. — There are a number of parasitic micro- 
organisms or infections which induce inflammatory changes but 
which give rise to tissue reactions of such special peculiarity that it 
is possible to conclude the agency of some one special infection 
from the nature of the inflammatory proliferation and the changes 
which take place in the products of the inflammation. Although 
the ordinary inflammatory irritants, the thermic, toxic and mechani- 
cal causes, act according to the intensity of their influence to cause 
now this now that type of exudate, there are some causative in- 
fluences which give rise to inflammatory reactions invariably having 
the same appearance and constant characteristics. These infectious 
agents are said to act specifically (that is peculiarly). Usually these 
types of disease are considered under special names, and will here 
be treated of in special chapters (v. Tuberculosis, Actinomycosis, 
Botryomycosis, Glanders). 



Parenchymatous Inflammation. 287 

Parenchymatous, Degenerative Inflammation. — The inflammatory pro- 
cesses almost exclusively run their course in the vascular connective 
tissue of the organ ; the other constituents, gland cells, muscles or nerves, 
take a more or less passive part. Inasmuch, however, as there may often 
be noted in the tissue elements constituting the organic parenchyma 
nutritive disturbances and regressive metamorphoses, either as primary 
changes produced by the cause of the inflammation, or as secondary 
alterations, due to the inflammatory process itself, it has become more or 
less customary to speak of such instances under the names parenchymatous 
or degenerative inflammation. Due to the action of irritants which 
primarily cause inflammatory changes in the interstitial tissue, there often 
occur such changes as cloudy swelling, fatty degeneration or necrosis in 
parenchymatous organs like the liver, kidneys or brain, of so marked a 
character that the real signs of inflammation in these cases almost entirely 
disappear, and perhaps can only be demonstrated by means of the micro- 
scope. The process and condition might well be summarily relegated, 
because of its principal features, to the degenerations. As the type of the 
degeneration is sometimes a complex one, made up of a number of forms 
of regressive changes, it is customary when some of the other features 
of inflammation coexist (hypersemia, swelling, induration) and the gross 
anatomical picture does not necessitate their separation, to employ the 
term "degenerative inflammation" for the combination of the two processes. 

[The editor feels that here too much stress is laid upon the passivity 
of the parenchymatous tissues in inflammation. They are, it is true, not 
the elements which strikingly react in the process, and their regressive 
changes are usually much more apparent than their active participation. 
Yet they do react and in practically the same way, as by proliferation, to 
some degree in this or that inflammatory process. A hepatitis is more 
apt, it is true, to exhibit the liver cells swollen and granular, yet occa- 
sionally there are found cells with karyokinetic figures in their 
nuclei ; direct nuclear division is not infrequently seen in the nuclei of 
muscle fibres in the case of myositis ; the axis cylinder buds in the 
inflammation caused by traumatic injury of a nerve, or the new growth 
of muscle spindles in the inflammation about a similar lesion of muscular 
tissue, argue to the same end. Proliferation commonly takes place in 
the epithelium of an inflamed mucous membrane or in a gland, and while 
parenchymatous cells probably take no part in ordinary encapsulation of 
foreign bodies, they may take part in elimination. They probably exert 
no unimportant part in the destruction or diminution of virulence of 
many toxic chemicals, as is a generally accepted function of the liver; 
and their aid in excretory elimination from the body of the same type 
of irritants, and in a minor measure of particulate elements, as unlit and 
perhaps harmful albuminous grannies, cannot be overlooked. That they 
are in a way phagocytic is evinced by their assumption of pigment 
material, changing it, it is true, in many cases by their metabolic activity. 
A microorganism may lodge upon some epithelial cell on a mucous sur- 
face, on a duct, or even in an acinus of some gland, and fail to he dis- 
lodged. The cell may react to the irritant microbic influences by pouring out 
a volume of secretion, possibly mucus, in which the microorganism is 



288 Inflammation. 

caught and with which it is carried away. Or the microbe may destroy 
the cell, which itself then becomes a further source of irritation. The 
cell may, it is true, desquamate from mere necrotic loss of adhesion to its 
basement membrane ; but at times — and too soon to permit of classing 
the phenomenon as anything but the result of an inflammatory prolifera- 
tion — one or more young cells grow up at its base and dislodge the cell 
with its bacterial burden, both being carried off by the fluid on the 
surface (as in a proliferative catarrh). As far as the proliferative feature 
of inflammation is concerned, it is essentially the same as the author has 
detailed in the chapter on Regeneration ; regeneration is one part of 
inflammation. Therefore it may be probably claimed that in some meas- 
ure, often insignificant, it is true, but in some cases clear and well marked, 
all the capabilities detailed as regenerative for parenchymatous cells are 
possible for inflammation. One should therefore be willing to accept a 
proliferative parenchymatous inflammation as well as the more striking 
degenerative inflammation, which alone may be inferred from the author's 
paragraph as characterizing parenchymatous structures in the inflammatory 
process. Moreover, from a theoretical standpoint, what has just been 
said may be understood as indicating that parenchymatous cells are 
capable of participating in all the ways ascribed to other fixed cells ; 
practically they do not manifest such ability in a degree comparable to 
that exhibited by the connective tissues. These features are considered 
further on by the author, who would exclude as normal some of these 
minor reactions.] 

The nomenclature and classification of inflammatory processes 
include considerations of the aetiology (traumatic, toxic, thermic, 
infectious inflammations), the duration of the process (acute, sub- 
acute, chronic) and the form of exudate and other anatomical fea- 
tures (fibrinous, serous, purulent, etc.). 

The scientific name (terminus technicus) used to express an in- 
flammation of an organ is constructed by adding to the root of the 
Latin or Greek word for the organ the termination itis (really from 
the feminine form of the major name ending in 77s) ; for example, 
■n-Xevpd, lining of chest cavity, irXevptT-qs , one suffering in the pleura, 
■n-XevpiTis ( supply vosds ) , inflammation of the pleura. In this way for 
example are built up such words as : gastritis, inflammation of the 
stomach; arthritis, inflammation of a joint; peritonitis, inflamma- 
tion of the peritoneum ; osteitis, inflammation of bone, etc. In 
case of inflammation of the serous covering of an organ the prefix 
"peri" is added to the name (-n-epi, about, around) ; in inflammation 
of the connective tissue alongside of an organ, the prefix "para" 
(irapa, alongside) ; for example metritis, perimetritis, parametritis. 
Special names are applied to some inflammations : pneumonia (not 
pulmonitis) for pulmonary inflammation; angina for inflammation 



Termination of Inflammation. 289 

of the soft palate and neighboring structures ; coryza, for nasal ca- 
tarrh; erysipelas for a special inflammation of the skin. 

As above stated inflammation is a local reactive process in which 
the mechanisms of the body underlying its protection from harmful 
influences and its compensation for disturbances are aroused to an 
especially intense activity. This defensive and compensatory func- 
tion exists even in normal conditions, as a vital cellular phenomenon 
of the animal body. Reactions of the same kind are almost all the 
time going on in the system ; here and there cells are dying and are 
being made away with by phagocytosis, and are being replaced by 
regenerative proliferation. Microorganisms are deposited at many 
points on a mucous membrane in communicating relation with the 
outside world and are rendered harmless by phagocytosis ; in the 
stomach and intestinal canal there often accumulate toxic sub- 
stances, formed from the food, which cause a hyperemia and 
are swept away by the increased secretion, or are taken up 
by the emigrated leucocytes (being quickly rendered inert in 
the liver) and only transiently excite some of the individual 
inflammatory phenomena. Insignificant and minor grades of 
inflammation are thus not infrequently induced, but these are 
not classed as inflammations. They are regarded as physiological 
phagocytosis, functional hyperaemia, physiological regeneration, each 
running its individual course ; they are not considered as disturb- 
ances. We only speak of inflammation when these reactive phe- 
nomena occur together and in unusually marked degree and when 
the causative injury or the reactive process itself is productive of 
functional faults in the affected part. 

Termination of Inflammations. — Since inflammation in many in- 
stances serves successfully to do away with useless and injurious 
materials and to restore the injured tissue or at least to replace 
faults with cicatricial tissue, it may be looked upon as a regulative 
and defensive effort of important use to the economy. In this adap- 
tive effort, with much propriety of comparison, the advancing leu- 
cocytes may be likened to mobilized troops or to a body of street 
cleaners ; but it cannot be said that the cells of the body pursue any 
fixed plan of procedure always under nervous control, but rather that 
the whole process is in reality the occurrence, it may be said the 
accidental occurrence, of phenomena of physiological motility and 
secretion of living protoplasm excited by external stimuli. The 
physiological component processes of inflammation arc the same as 
the cellular functions of phagocytosis and secretion which take 
place in digestion, the result of mechanical and chemical excitation, 



290 Inflammation. 

peculiar, however, in that these cellular activities are not confined to 
any single organ but extend to all the organs, to the vascular con- 
nective tissue framework of all parts of the body. 

The favorable or unfavorable outcome of inflammation depends 
upon accidental factors, upon the nature and mode of action of the 
causative agents, upon the location of the part injured and the de- 
gree of functional disturbance which the inflamed organ experiences. 
Of the individual reactions which in combination constitute inflam- 
mation, it can be accepted that phagocytosis removes structures 
killed by harmful foreign bodies, that the exudation exerts a di- 
gestive action upon and washes away injurious substances, that the 
blood plasma (and possibly too a secretion given off from the leuco- 
cytes) supplies antitoxic substances, and that the tissues are brought 
into a state of regenerative ability by the increased nutritive supply. 
All of these factors combine to bring about compensation for the 
influences of a variety of harmful agencies. When the irritant is 
removed or encapsulated the condition of special stimulation ceases 
and the inflammation ends in resolution, because no more fresh cells 
advance into the area and those which have previously escaped from 
the vessels either break down and are reabsorbed as detritus with the 
other parts of the exudate by the veins and lymphatics, or, in case 
they retain their power of movement, pass off to other places toward 
which they are attracted by nutrient matter. 

The inflammatory process cannot invariably bring about com- 
plete regeneration of destroyed tissue ; as a rule onlv the connective 
tissue is fully replaced, the specific elements which are lost, as 
glandular or ganglionic cells, not being reformed. It is in this way, 
by the formation of connective tissue to occupy the space of a lesion, 
that inflammation brings about healing of the lesion. The inflamma- 
tory connective tissue growth which paves the way for encapsula- 
tion of foreign bodies and demarcation of dead tissue is in the same 
way to be regarded as an attempt at healing. 

However, there are also disadvantageous features connected with 
inflammation. Adhesions between organs, the occupation of cavities 
by masses of exudate, as in the lung or pleura, exudative effusions 
in the brain or in the kidneys, occasion functional disturbances, 
which, depending on the importance of the affected organ, may 
threaten the life of the subject ; and inflammation may terminate in 
death. This does not, however, essentially alter the conception of 
inflammation as a defensive effort. Ribbert compares it to an 
army, which, it is true, is in the main a valuable organization, but 
which may fail at times to overpower a stronger enemy or which 



Tuberculosis. 291 

may from the cost of organization and armament, financially ruin 
a land. The fatal termination and the local disadvantages of the 
disease are, strictly speaking, not attributable to the inflammation 
but to the causes of the inflammation. 

Tuberculosis. 

Tuberculosis is a contagious infectious disease having a very 
wide distribution among man and the domestic animals, caused by 
the tubercle bacillus discovered by Robert Koch in 1882, and char- 
acterized anatomically by the formation of minute nodular inflam- 
matory foci (tuber culum, a small node) which uniformly undergo 
necrotic disintegration and by their progressive increase destroy the 
tissue involved by them. 

This malady, the most common of all diseases, manifests itself 
in man generally as a pulmonary affection of years' duration, causing 
pulmonary wasting and consumption (phthisis, ivomcpeiio, to waste, 
consume) , but also producing painful destruction of bones and joints, 
ulceration of the intestines, and tuberculous disease of the lymph 
nodes, brain and other structures. Year after year tuberculosis car- 
ries off over a million people in Europe, or nearly three thousand 
every day, and must therefore be regarded as the most deadly of all 
plagues, decimating the populace, and hurrying to death the effi- 
cient youth and destroying the earning capacity of families by the 
tedious course of the affection and death of their members. 

The disease is no less a calamity to the cattle industry. Among 
domestic animals cattle and swine are most frequently affected ; 
ten, twenty, yes eighty per cent, of the cattle brought to the larger 
stock yards in some districts are diseased. The financial losses oc- 
casioned by the affection of so many animals may be estimated by 
hundreds of thousands of dollars annually, for these include 
such varied elements as loss of weight and forced slaughter, impair- 
ment of milk production and of edibility of the meat, and sterility or 
transmission of the disease to offspring. Tuberculosis in cattle be- 
comes doubly important when the danger to human health is con- 
templated, because the milk of animals with tuberculosis of the udder 
can transmit the disease to children and adults. 

The effort to overcome this infectious disease, which has been 
continually on the increase during recent decades in man and in 
animals, has therefore come to be one of the most important aims of 
medicine, an object of municipal and national thought, and a matter 
of interest both to the community and to the individual 



292 Specific Inflammations. 

The communicability of pulmonary consumption was suspected 
even by the physicians of antiquity (Hippocrates, Isocrates) and 
had obtained some credence among the laity. More or less energetic 
measures (burning of beds and linen used by consumptives, disinfec- 
tion of furniture and dwellings by means of smoke, etc.) were 
practiced as early as 1750 at Nancy, 1782 at Naples and about 
the beginning of the nineteenth century were ordered and carried 
out by authority of court, but were without result because of 
their insufficiency to remove all the factors of infection. 

According to Nocard* phthisis is said to have been declared a 
.contagious disease in one of the Gothic laws. 

Under the influence of the erroneous teaching of Broussais that 
phthisis arose spontaneously as a result of meteorological conditions, 
social misery, etc., and the widely spread mistaken conception which 
prevailed after the discovery of the tubercle bacillus to the effect 
that this disease germ is omnipresent (ubiquitous), efforts toward 
prophylaxis remained restricted. With the idea that predisposition 
was the most important fault it was considered impossible to root out 
the evil ; or it was held that the difficulties involved in the campaign 
were insurmountable because of the impracticability of enforcing 
the necessary rules of procedure. The old suspicion of the conta- 
gious character of the disease received the first important confirma- 
tion in the studies of Klencke (1843) an< ^ Villemin (1865-1868), 
the latter proving by a series of positive experiments the inocula- 
bility of human tuberculosis and pearl disease of cattle into rabbits, 
etc., and establishing the identity of animal and human tuberculosis. 
Thereafter numerous investigators interested themselves in Ville- 
min's teaching and repeatedly carried out similar experiments, some- 
times confirming, sometimes opposing his results. (For details cf. 
writings of Johne and Nocard.) With the discovery of the tubercule 
bacillus by Robert Koch and the ingenious labors of this German 
investigator, which have completely unraveled the aetiology of tuber- 
culosis of man and animals, all doubts as to the nature of the af- 
fection disappeared. Koch succeeded in discovering and demon- 
strating the tubercle bacillus by a special method of staining devised 
by him ; and it is always possible by means of this method in case of 
tuberculosis to recognize the tubercle bacillus in diseased parts and 
material discharged from them both in man and in animals. This 
microorganism presents itself as a rod-shaped microphyte, from two 
to four micromillimeters in length and from three to five-tenths 

* E. Nocard, Les Tuberculoses Animales ; Encyclopedic Scientifique des Aide 
Memoire. Paris : Masson. 



Tuberculosis. 



293 




Tubercle 
mucus 
1,000. 



Fig. 61. 

bacilli ii 
of cow 



bronchial 
X about 



micromillimeters in width (about one-fourth to three-fourths the 
diameter of a red blood corpuscle). Koch also pointed out the possi- 
bility and methods of growing the tubercle bacillus in artificial nutri- 
tive media outside the animal body; and thousands of experiments 
have contributed to the proof that by inoculation of artificially culti- 
vated germs tuberculosis may be reproduced in all its forms in any 
of the warm-blooded animals. 

The tubercle bacillus does not 
grow free in nature ; occurring only 
where it is deposited with tuberculous 
discharges. It multiplies in this cli- 
mate but not outside the animal body 
and only within the organs of the 
animal or human economy. In the 
free state the germ of tuberculosis 
may retain its vitality and virulence 
when dried and in the dark for a 
long time (more than a year) ; but a 
variety of conditions may serve to 
render the infectious material harm- 
less or destroy it. Sunlight, for ex- 
ample, will kill the organism in as short a time as two to four 
hours and even diffuse daylight will destroy it. Rain has a favor- 
able influence in washing away the vehicle of the contagion and 
thus exposing it to light; a temperature of 50°-70° C. developing 
in manure will also kill it. 

For such reasons tuberculosis must be regarded as a true con- 
tagious affection. Its transmission from one human being to another 
occurs chiefly from the expectorated sputum, which, dried and blown 
about as dust, gains access to the pharynx and air passages by in- 
halation, sometimes a portion being swallowed and finding its way 
from the intestines into the tissues or sometimes infecting the 
pharyngeal tissues and air passages. Tiny drops of saliva or 
mucus containing the organism may sometimes be discharged in 
talking or sneezing and in case these are directly inhaled by a 
second individual, or if they fall upon the food and are ingested 
with it, they may give occasion for development of tuberculosis. 
The number of tubercle bacilli in such expectorated matter may be 
enormous ; in a single drop of microscopic size there may be hun- 
dreds and it has been estimated that one consumptive human being 
may give off seventy-two hundred millions of tubercle bacilli in the 
course of a single day (Heller). 



294 Specific Inflammations. 

The contagion is carried from animal to animal in the same way. 
Cattle and hogs affected with pulmonary tuberculosis discharge 
bronchial mucus loaded with tubercle bacilli by their coughing ; and 
this is inhaled as fine spray-like droplets by other animals standing 
near by, or falls upon the fodder or into the water and with these 
substances may gain entrance to a new animal body. One of the 
most important sources of tuberculous infection both for man and an- 
imals is the milk of cattle affected by tuberculosis of the udder; 
milk from such a source may, as shown by Bangs, remain apparently 
normal even for weeks though it contain millions of tubercle bacilli. 
If swallowed in raw state, as used in the feeding of calves and pigs, 
such milk gives rise to infection of the body by way of the alimen- 
tary canal and chyle vessels, as proved by experimental feeding. 
The general milk from a dairy may become infected if there be 
but one cow in the stalls with tuberculosis of the udder, provided 
that cow be milked with the rest and her milk mixed with that 
from the other cows. 

Again the intestinal discharges of consumptive animals contain 
the infection, either because these animals, as is often the case, 
have tuberculous ulcers of the intestine, the bacilli from which be- 
come mixed with the excrement, or because the animals swallow 
their pulmonary expectorate and the bacilli pass through the bowel 
without being all destroyed. The vaginal discharge from cows with 
uterine tuberculosis furnishes another source of infection. The 
straw saturated with these infectious discharges, should it happen 
to be eaten by other cattle with their fodder, may serve as a means 
of transmission of the disease. Occasionally infection occurs in 
coition, as "the vaginal secretion may be carried from one animal to 
another by the male, or the latter, when tuberculous, may transmit 
his own bacilli in the spermatic fluid. Tuberculous infection of 
cutaneous wounds is rare among animals, although occasionally in 
man post mortem section of tuberculous organs gives opportunity 
for this mode of infection. 

The horse is usually infected with tuberculosis by eating straw 
(soiled with the tuberculous discharges of cattle) ; the dog often 
by licking up human tuberculous sputum ; the cat by drinking tuber- 
culous milk. The disease develops in fowls where the latter have 
opportunities to pick up human sputum or tuberculous discharges 
from horses, cattle or hogs ; the excrement of chickens already 
affected with intestinal tuberculosis, however, affords the greatest 
chance for the infection of the other feathered inhabitants of the 
premises (soiling of food, ground, etc.). 



Tuberculosis. 295 

Tuberculous human beings and animals are sources of further 
infection only as they throw off materials containing tubercle bacilli. 
The foci of the disease which exist within the animal, shut off from 
the exterior, as tuberculous lymph glands, do not give off bacilli 
in such a way that they may be transmitted to another animal. 
For example, the milk of cows which do not have tuberculosis of 
the udder is harmless even though there are tuberculous lymph 
glands and serous membranes in the animals ; the meat of a tuber- 
culous animal is free from danger as long as it does not contain 
actual tubercles or as long as the lymph nodes situated in the flesh 
remain free from tubercle bacilli. (For further details consult 
Ostertag: Zeitschr. filr Fleisch- und Milchhygiene, 1890-1903.) 

Concerning the question of inheritance of tuberculosis, observa- 
tions running over a number of years upon the condition of calves 
born of tuberculous cows, with control by tuberculin injections 
and slaughtering (Bang), as well as a series of experiments upon 
pregnant tuberculous guinea pigs (Gartner), give positive informa- 
tion. Tuberculosis may be acquired through the placenta. Many 
examples of this have been found in newly born calves and children, 
and occasionally too in the miscarried foetus. In such cases the 
liver and periportal lymph nodes are invariably involved and the 
disease is apt to be more or less distributed to other lymph glands 
and organs. When it has been possible to investigate the mother 
of the tuberculous offspring, invariably a tuberculous affection of 
the uterus and sometimes of the chorion were found. The tubercle 
bacillus is scarcely likely to pass directly from the blood of the 
mother to the foetus (the blood is separate in the two parts of the 
placenta) ; but if during pregnancy the uterus should become in- 
volved by tuberculosis (focal, as in one cornu) the tubercle bacilli 
find their way into the placental milky humor and penetrate the 
foetal placenta, and then pass with the blood of the umbilical vein 
to the liver of the foetus. In this way the latter is born into the 
world a subject of tuberculosis ; but it is possible that after birth 
the disease may progress very slowly and remain latent for months. 
A conceptional or germinal infection, that is through the ovum or 
spermatozoon, is so improbable that it may be said to be entirely im- 
possible. Supposing the possibility that a fertilized ovum could be 
infected by tubercle bacilli, it would die from the caseating influence 
of these germs long before it could develop into an embryo, or else 
the embryo in its earliest stages of germ vesicle and formation 
of the blastodermic layers would already be but a degenerating mal- 
formation. When it is remembered that of the millions of sperma- 



296 Specific Inflammations. 

tozoa which enter the female genital canal in coition only a single 
one passes through the micropyle of the ovum, it cannot but be a 
strange coincidence that just this very one should carry with it a 
tubercle bacillus. (Tubercle bacilli in the sperm are scarcely likely 
to adhere to the spermatozoa but are more likely to remain in the 
fluid.) And, too, if the fertilizing spermatozoon accompanied by 
a bacillus should penetrate into an ovum the bacillus as it multiplied 
would at once seriously interfere with the process of multiplication 
of the copulated cells and quickly put an end to the embryonic 
germ by coagulation necrosis. The assumption that tubercle bacilli 
may somehow lie dormant in an ovum in course of embryonic de- 
velopment, and later when the fcetus has been formed start to mul- 
tiply, is without foundation and is in contradiction to all our knowl- 
edge of the growth of vegetable microorganisms in the animal body. 
[Mafucci's experiments in chicken eggs (Centralbl. f. Bakt. u. 
Parasitenk., 1889, p. 237.) are usually offered as contradicting this 
contention. He inoculated eggs with tubercle bacilli and then in- 
cubated them. Out of eighteen eggs he obtained one dead and 
eight living chicks. He was unable to find tubercle bacilli in the 
dead chick, and examining the unfertile and rotten eggs which 
failed to hatch he was unable to be satisfied of any growth of the 
tubercle bacilli In them. His chicks were at first apparently healthy, 
but later died with well defined tuberculous lesions. That latency 
df infections is possible in relation with embryonic development is 
also indicated by the transmission of the psorosperms of pebrine, 
pointed out by Pasteur, through the ova of silk worm moths to the 
silk worms, which at first seem healthy but soon die from the dis- 
ease.] 

Attempts to prove from genealogical tables and statistics that 
there is a true hereditary transmission of tuberculosis from parents 
to offspring must always meet with the objection that children or 
calves may be born free from the disease and may acquire the tuber- 
culosis in the first years of their lives from living in the presence of 
their tuberculous parents. The above principal modes of trans- 
mission of the tuberculous virus have been proved by great num- 
bers of experiments. With human tuberculous sputum as well as 
material obtained from tuberculous foci of the lungs, liver, lymph 
nodes, intestine, etc., human or animal, and, too, with pure cultures 
of tubercle bacilli, typical tuberculous disease can be caused either 
by feeding, inhalation, or by subcutaneous, intraperitoneal or intra- 
venous injection in all susceptible species of animals. There are, 
however, certain differences, or rather dissimilarities, in pathogenic 



Tuberculosis. 297 

ability in tubercle bacilli derived from human beings and from 
various types of animals, referable to the source of the virus. For 
example, as shown by R. Koch and Schiitz in a long series of experi- 
ments, and even earlier by Putz (1882) and Smith (1896), it is not 
as a rule easy to render cattle, sheep and swine tuberculous by 
using tubercle bacilli from a human source (even in case of inoc- 
ulation of large quantities) ; and it is also difficult to infect birds 
with tuberculous material derived from man or mammals. These 
negative results at first caused doubt as to the identity of the tuber- 
culosis of all individuals. However, it was recognized that no dis- 
tinct line of difference could be drawn between the organisms, for 
even a few positive results were sufficient to show the identity of 
the affection in man and in animals. Positive cases of the kind re- 
quired have been obtained in such abundant number and from ex- 
periments of indisputable accuracy that the possibility of infecting 
man with bovine tuberculosis and of the transmission of human 
tuberculosis to the domestic animals cannot be denied. Besides the 
older experiments of Bollinger, Klebs, Chauveau and the later ones 
of Sidney Martin, Frothingham, Arloing, de Jong, Stuurmann, 
Thomassen, Prettner, Klebs and Rievel who were successful in 
inoculating cattle with tuberculous virus from man, the examples 
collected by Johne, Ostertag and Nocard and Leclainche of wound 
inoculation in man, occasionally actually occurring in the 
course of slaughtering operations and meat inspection, speak 
strongly for the idea that bovine tuberculosis is an infection of no lit- 
tle importance to man. Important contributions have also been made 
in this connection by Johannes Fibiger and C. O. Jensen, going to 
show that tubercle bacilli virulent to man may also be highly viru- 
lent to cattle, and confirming the belief that many cases of intestinal 
tuberculosis in children are properly attributed to the ingestion of 
cow's milk containing tubercle bacilli, von Behring arrives at the 
same conclusion, finding that some strains of tubercle bacilli obtained 
by culture from human source possess high grade of virulence for 
cattle while other strains have no pathogenic influence for cattle 
at all. Further the observations made by Eberlein and Cadiot, in- 
dicating the acquirement by man of the infection from tuberculous 
parrots and the rather common transmission of the disease to parrots 
from consumptive human beings, as well as the transmissibility by 
inoculation of bovine tuberculosis to apes, proved by Nocard, force 
the assumption of an etiological relationship of the disease or o\ a 
family identity of the tubercle bacilli of heterogeneous derivation, 
[Recently Koch has brought forward anew the idea of specific dif- 



298 Specific Inflammations. 

ference between the bacilli of human and bovine tuberculosis, but 
has met strong opposition at the hands of a large number of stu- 
dents. In this country Ravenel and Pearson have shown distinctly 
the identity of the microorganisms; and the work of these investi- 
gators in inducing immunity in cattle against bovine tuberculosis 
by vaccination with cultures of human tubercle bacilli of. low viru- 
lence is of extreme significance.] 

The variations in pathogenic power exhibited by the bacilli ob- 
tained from different sources find their explanation in the adaptation 
of the organisms to the different animal bodies. It is obvious and 
reasonable that, in case of transmission of consumption which has 
been going on for centuries from one human being to another, in 
which the tubercle bacilli of every generation always grow ex- 
clusively in the human body, the organisms may come to adapt 
themselves to the conditions of nutrition which the human system 
supplies to them, and that they attain their greatest infectious power 
for it and find more difficulty of growth in another type of animal 
body. In the same way tubercle bacilli which have passed through 
many generations in the bodies of herbivora become as it were accli- 
mated, and are best able to infect again an animal of the same species. 
The tubercle bacilli of birds (whose normal body temperature is 
known to be 4i°-42° C, and whose tissues and fluids from their 
known resistance to tetanus virus, etc., must have totally different 
affinities from those of mammals) are particularly changed in their 
biological characteristics so that they seem to be of a totally different 
stock ; and, too, it is difficult to successfully induce a growth of 
tubercle bacilli from mammals in the avian body. However, now 
and again birds have been rendered typically tuberculous by inocu- 
lation with mammalian tuberculosis, and conversely horses (No- 
card) have been infected with avian tuberculosis ; and therefore the 
differences may be considered as merely expressions of a varia- 
bility of biological properties. We must consider tuberculosis of 
man and the animals as caused by one and the same infectious 
agency, which from long transmission through one particular animal 
species may develop definite varieties and strains of uneven patho- 
genic power. (For further details consult Nocard-Leclainche : Les 
Maladies Microbiennes des Animaux. III. Ed., Paris, 1903.) 

The anatomical lesions determined by the tubercle bacillus are 
as follows : After being conveyed into the body of a man or ani- 
mal the tubercle bacillus multiplies into masses, provided it finds a 
suitable soil at the temperature of the animal ; penetrates by growth 
into the tissues and is carried more widely by the wandering 



Tuberculosis. 



299 



cells. Its deposition, along with the toxine which it produces, 
causes a reaction on the part of the tissue as about a foreign 
body, in which, however, the special toxic action of the micro- 
organism takes part and gives rise to coagulation necrosis. 
The first evidence of reaction as shown by the studies of 



/'■' "'.'> 



■rsa/fca 



;.'•■■*. 



/ 






-- ■ 



~* 











Fig. 02. 

Embolic miliary tubercle from lung of horse (after .Tohne) ; (/, giant cells; b, 
cheesy centre; c, small as yet not caseated tubercle; </, surrounding pulmonary 
tissue ; X 90. 



Baumgarten, Johne and others is the appearance of karyokinetic 
figures in the fixed connective tissue cells and endothelial cells, 
and side by side with this an increase of the latter. The prolifer- 
ating fibroblasts, among which usually giant cells occur, surround 
the tubercle bacilli ; and further out immigrating leucocytes 



300 Specific Inflammations. 

or lymphocytes collect about the - periphery of the focus occupied 
by the bacilli. In this manner a rounded cellular nodule is 
formed, at first microscopic in size, but later increasing in bulk to 
that of the head of a pin or millet seed, and known when visible 
to the naked eye as a submiliary and miliary tubercle (milium, a 
millet seed). It is of a gray, opal-glass-like color, with a dead- white 
to yellowish point in the centre which indicates the early stage of 
coagulation necrosis (caseation). [The central cells of the unde- 


















J 


V 




$h 










% 














' - 




vi*? v 4 




Vv3 










v}Vv" 




i V'* «** 










■*/j|j? 




! 


•% 








//■? 




« * 




■'- r 






1 Q 















Fig. 63. 

Miliary tubercle (higher magnification) ; a. giant cell: b. caseated centre; c, zone 
of epithelioid cells ; d, zone of lymphoid cells. 

generated miliary tubercle, in and among which the tubercle bacilli 
are found, are of uncertain origin. They are commonly spoken of 
as endothelioid or epithelioid from the comparatively large amount 
of protoplasm and the rather pale and vesicular nucleus, and are 
distinguishable by these features from the ordinary fibroblasts. They 
vary in shape but are more commonly of a rather flattened spindle 
form than otherwise. The author's view that these are essentially 
the same as young connective tissue corpuscles and the product of 
proliferation of the fixed connective tissue cells is accepted by some ; 



Tuberculosis. 



301 



others believe, as the name enclothelioid would suggest (epithelioid 
synonymous and used rather to indicate the general epithelial-like 
appearance than referring to the source of these elements), 
that they are derived from the endothelial cells, mainly those of the 
lymph spaces in which the bacilli are lodged. The true lympho- 
cytic nature and origin of the peripheral zone of small mono- 
nuclear cells is commonly accepted. There is considerable uncer- 
tainty as to the mode of formation of the giant cells. According to 
some they are the result of the fusion of cells undergoing hyaline 
or coagulative change ; and are therefore looked upon by these per- 
sons as evidence of beginning or advancing degeneration in the 
focus. From this standpoint a miliary tubercle when exhibiting one 
or more giant cells in its structure is essentially a degenerating 
tubercle. Others believe that they are the result of inefficient proto- 
plasmic division of growing cells, in other words are of a prolif- 
erative type of development and not of the significance just indi- 
cated. Tubercles of fresh and undegenerated structure are com- 
monly called gray tubercles ; older and degenerated ones, yellow 
tubercles.] 

The site of formation of the tubercle is in the connective tissue 
framework of the affected part or in the walls of the blood vessels 
and in the lymphatic foci of the tissue. This gives the cellular pro- 
liferation a connective tissue frame work or reticulum as a skeleton, 
which may, however, be in part, too, a product of the fibroblasts 
and giant cells, which of course also supply an intercellular sub- 
stance. Although endothelial cells also take part in the formation 
of the cellular nodule these do not develop into vascular buds, and 
the miliary tubercle is avascular. The endothelial cells in their pro- 
liferation may occlude the lumen of the capillary vessels ; and more- 
over by the growth of the cellular mass the vessels may be com- 
pressed. In contrast to these factors the tuberculous reaction may 
also present itself as a diffuse proliferation, without production of 
sharply defined nodules and with the formation of new blood ves- 
sels. In this case there is found a soft, gray or grayish red layer, 
especially seen in serous surfaces (bovine heart), which is not likely 
to undergo more than a slight caseation, or, if it does, only after 
considerable time. This, too, always has a distinct granular appear- 
ance looking as if caused by fusion of closely set miliary tubercles. 
This diffuse growth is due to the fact that separate groups of tuber- 
cle bacilli do not here occur as the centres of nodular circumscribed 
cellular collections, but that large numbers of the organisms are 
scattered all through the tissue. 



302 



Specific Inflammations. 



This inflammatory reaction is not characterized merely by the 
marked collection of wandering cells in the tuberculous tissue, but 
also by actual exudation upon the surfaces of the organs. Especially 
in the pleural cavity of dogs this may be seen as a marked sero-cel- 
lular collection of fluid, the result of a purely tuberculous granula- 
tion ; and in various tuberculous tissues microscopic examination 
shows the appearance of thread-like {fibrinoid, Schmauss and Al- 




Fig. 64. 
Miliary tubercle in the liver of a dog (slightly magnified) 



brecht) coagulation masses lying between the proliferating and de- 
generating cells and suggesting an exudative origin. 

With the proliferation of the tubercle bacilli and their extension 
into the adjacent tissues the amount of toxic material given 6fT 
by them and taken up by the lymph becomes increased. The casea- 
tion is to be ascribed to the influence of this substance ; and in pro- 
portion to the latter the caseous areas grow larger as the reactive 
cell proliferation increases the size of the nodule. At first puncti- 
form or streaked cloudy specks appear and the necrotic foci fuse 
into progressively larger and larger, dry, anaemic or (after a fatty 



Tuberculosis. 



303 



disintegration) into soft, partly purulent, partly caseous areas of 
very variable size. Such necrosed parts may become impregnated 
with lime salts (especially .in.' cattle) and eventually assume a 
chalky, plaster-like or sandy appearance. 

Just as in chronic productive inflammation the fibroplastic tissue 
is changed into a firm cicatricial mass, the proliferated connective 
tissue cells of a tubercle, are also able to assume a genuine fibro- 




Fig. 65. 
Fungous tubercle with giant cells (without caseation) from the larynx of a cow. 

plastic function, particularly in the formation of a fibrillar matrix 
and may thus give to the tubercle a firm fibrous character. 

It may therefore be appreciated that the anatomical forms of 
tuberculosis vary considerably according to the tissue predisposition 
in the different animal species, and the extent and duration of the 
process. The principal forms are: miliary tuberculosis, tubercu- 
lous ulceration, tuberculous cheesy infiltration, tuberculous ca; ities, 
fungous granulomatous tuberculosis (or tuberculoma) . 

The miliary tubercle, the earliest product of the reactive process 
of the disease, as already stated, appears as a gray or yeljowish-red 



304 



Specific Inflammations. 



nodule of the size of a pin head or millet seed ; these may be single 
or multiple, may be scattered widely over a large surface and dis- 
seminated in the same way throughout the organic substance, par- 




Fig. 66. 

Tuberculosis of liver of a pheasant. The tubercles show a sharp limitation of 

the cheesy centres. 




Fig. 67. 

Tuberculosis of liver of dog. 



(After Cadiot.) 



ticularly on serous surfaces and in the lungs. They develop to visible 
size within from fourteen to thirty days after infection; the micro- 
scopic stages at the very beginning may be made out as early as 
from five to ten days. If the organ is the seat of submiliary or 



Tuberculosis. 



305 



miliary nodules alone, all of the same age, that is of uniform size, 
it is said to be involved by acute miliary tuberculosis. With local 
multiplication of the tubercle bacilli, the nodules enlarge to the size 
of a lentil, pea or nut, these larger forms usually showing their 
origin from fusion or conglomeration of smaller miliary tubercles. 
This condition constitutes what is known as chronic miliary tubercu- 
losis. On serous surfaces the formation of nodular masses gives 
rise to the so-called pearl disease. 

The tuberculous fungous granuloma is the result of a progres- 
sive formation of cellular nodules and their profuse growth on free 
surfaces ; it is chiefly met with in 
the thoracic serous membranes and 
peritoneum and sometimes, too, in 
the intestinal mucous membrane. By 
the synchronous development of the 
nodules and of a vascular connective 
tissue growth, there may be produced 
grayish-white, grayish-red and yellow- 
ish-red tumor-like masses from the size 
of an egg to that of a fist, which are 
piled up about and over each other as 
large excrescences, covering consider- 
able surface areas and reaching per- 
haps a weight of from twenty to forty 
kilogrammes. Caseation of these tu- 
berculomata, which also occasion adhe- 
sions of the serous surfaces, at first 
appears in punctiform foci and in 
small spots in the granulation tissue, 
as yellow or light yellow opacities, and Fi s. 68. 

can advance to complete transforma- mee ^ e i a t ^T a ^nSaM bi !S^ 
tion of the whole bunch of nodules into face of smali int e stine -) 
a mass which on section looks like corn-bread, yellow, hard, gritty 
and partly calcified. 

Tuberculous ulcers, especially in the bowel, larynx and bron- 
chial tree, result from the maceration and disintegration of the 
caseated parts as well as from a purulent softening of the tuber- 
cles developing in the mucous surfaces (lymph follicles). These 
areas of tissue destruction are circular or oblong, shallow or some- 
times a millimeter in depth, as large as a lentil to a little over a 
centimeter in diameter, or in the bowel reaching perhaps the length 
of a finger and two fingers in breadth. The base of the eroded spot 




306 



Specific Inflammations. 



is mottled grayish-red and yellowish, and minute tubercles can be 
distinguished growing On the base and margins of the ulcer. The 
base looks granulated ; the bordering wall of mucous membrane is 
thickened and sometimes a marginal circlet of projecting miliary 
tubercles can be seen about it. 




Fig. 69. 
Chronic miliary tuberculosis and lobular tuberculosis of lung of horse. 

Cheesy tuberculous infiltration, apt to be found involving lymph 
nodes or lungs, changes the affected area of the organ into a very 
large, hard, densely caseated mass of a yellowish white to chrome 
yellow color, reminding one much of the boiled yolk of an egg. 
This change is apt to be very diffuse and is generally accompanied 



Tuberculosis. 



307 



/ 






by the formation of a firm bacony connective tissue of the nature 

of a confluence of fibrous tubercles, or in other words a 

chronic tuberculous inflammation. Lymph glands, the seat -of. 

tuberculous infiltration, may grow to enormous 

masses as thick as an arm, or the size of loaves of 

bread. Bunches of tuberculous pulmonary lobules 

are converted into dry necrotic masses as big 

as a fist and comparable in appearance to Edam 

cheese or Swiss cheese ; or sometimes whole 

lobes are changed into large, lumpy masses, 

hard, weighing over a kilogram, and riddled 

with points of cheesy softening. 

Tuberculous cavities, developing in the 
areas of cheesy infiltration, are cavities varying 
from the size of a nut Or fist to a span [a span is 
nine inches] and a half in diameter.- They con- 
tain a greasy, caseous and slimy mass of detritus 
and are limited by a wall of pale, indurated 
fibrous tissue or by the tissue of the organ modi- 
fied by the different color shades given by the 
tuberculous inflammation, and giving rise to the 
cavities by degenerative changes affecting it. 

These more important types of tuberculous 
changes* may combine in various ways and 
there are apt to be, too, special modifications due 
to peculiarities of the tissues in the various types 
of animals. While cheesy areas in cattle usually 
have an intense yellow color, in horses and car- 
nivora they are apt to be whiter and sometimes 
quite milky. They are not at all uniform in 
consistence, sometimes dry and cheesy, some- 
times soft and pultaceous or possibly broken 
down into a pus-like fluid. Caseation may in 
some instances be absent and the tubercles 
may be of a more cellular character, look- 
ing like the tissue of lymph glands ; or they may become hard 
and fibrous (in horse). 

The entrance of tubercle bacilli into a tissue generally occurring 
at places where lymph nodes lie exposed (pharynx, intestine) at first 
causes a primary local tuberculosis at the point of infection. How- 

Aull.. 




Fig. 70. 

Tuberculous rib of 
cow (fresh sec- 
tion). 



♦For detailed examples cf 
Stuttgart, 1903. F. Bnke, 



Kill, L<inbiicii (I. %pee, path- \nni. 



1 1 



3o8 



Specific Inflammations. 



ever the point of infection may escape involvement provided the 
tubercle bacilli are rapidly carried onward by the lymph, under 
which circumstances the tuberculous inflammation may first show 
itself in the lymph glands. After feeding tuberculous material to 
hogs the mucous membrane of the intestine is uniformly unaffected 
and the disease primarily occurs in the mesenteric lymph nodes. 
[Ravenel has produced a similar primary involvement of the lymph 
nodes of the mesentery in dogs by feeding the tubercle bacilli 
rubbed up in butter, having previously starved the experiment ani- 
mal for a time.] After being taken up by the chylous vessels the 
tuberculous virus passes into the blood by way of the thoracic duct 
and thence into the lungs, and after traversing the lesser circulation 
is carried to all of the organs. The different organs do not all show 




Fig. 71. 
Portion of lung of horse showing miliary tubercles and tuberculous infiltration. 

a uniform predisposition to the influences of the bacilli, that is, 
they do not all offer equally favorable conditions for the nutrition 
of the microorganisms. The lungs, lymph glands and especially the 
general lymphatic tissues (bone-marrow, spleen), are places where 
the bacillus most readily lodges. For this reason the lungs may 
become the seat of the primary involvement after feeding tubercle 
bacilli to an animal, and the existence of the pulmonary affection 
is by no means to be looked upon as indicating that infection took 
place by inhalation. 

The primary, and in fact the only tuberculous focus may be en- 
countered in the interior of bones, or in lymph glands or the tes- 
ticle. In such instances isolated tubercle bacilli which have gained 
access to the blood may have been caught and lodged in any such 



Tuberculosis. 



309 



situation and there caused the disease. Generally the whole 
path traversed by the bacilli is mapped out by foci of the 
disease, first the primary local focus and after it the neighboring 
regional infection, then the secondary tuberculosis of the lymph 
glands which receive the lymph from the affected part. From the 
latter along the lymphatics or, as above mentioned, by the chylous 
route, the germs find their way into the blood or may directly pene- 
trate through the walls of the blood vessels in the course of the tu- 
berculous proliferation ; and then, depending upon whether many or 
only isolated bacilli are carried to the various organs, there is pro- 




Fig. 72. 
Uterine tuberculosis, from cow. 

duced a metastatic, hematogenous, embolic, multiple or dissemi- 
nated miliary tuberculosis of the lungs, brain, liver, kidneys, etc. 
Muscle (meat) shows the ^greatest degree of resistance, usually only 
the intermuscular lymph nodes being affected. This general inva- 
sion of the tuberculous virus with its resulting tuberculous foci is 
spoken of as general tuberculosis. The metastatic miliary nodules 
of course increase in size, and by confluence and advancing casea- 
tion cause progressive extension of the tuberculous destructive 
changes. Finally, too, contact infection along mucous membranes 
occurs from the convection of the germs over the surface with its 
fluid secretion, as infection of the larynx from the lungs, of the 
vulva from the uterus, etc. 



310 Specific Inflammations. 

The symptoms of tuberculosis appreciable during the life of the 
affected animal vary widely with the different situations of the pri- 
mary disease. Fuller details than space here permits are contained 
in the publications of Johne, Siedamgrotzky, Albrecht, Lydtin and 
other authors and particularly the text books of Friedberger and 
Frohner, Dieckerhoff, Csokor, Nocard-Leclainche and Moussu. 
Pulmonary tuberculosis manifests itself by a remittent fever, im- 
paired condition of nutrition in spite of good appetite, induration 
of the skin (hide binding) associated with loss of subcutaneous 
fat, rapid and difficult breathing, a feeble dry cough, impairment of 
percussion resonance and the presence of rales. Chronic flatulence, 
as pointed out by Johne, is a frequent evidence of the existence of 
greatly enlarged tuberculous mediastinal lymph glands from pres- 
sure on the gullet, interfering with belching. Tuberculosis of 
the mammary gland may be recognized by a gradually increasing 
induration and diffuse painless swelling in one, two or all parts of 
the udder, with synchronous enlargement of the supramammary 
lymph nodes. In this condition the milk may be quite normal in 
appearance for weeks or at least only changed in that it 
is more watery, thinner (in the last stages only may one notice the 
admixture of small flakes of a pus-like appearance). Superficial 
lymphatic glands, as the retropharyngeal, often become very large 
in tuberculosis, hard and nodular. Tuberculosis of the brain com- 
monly shows the violent symptoms of meningitis (excitement, un- 
consciousness). In tuberculosis of the ovary symptoms of sexual 
desire are sometimes observed. Tuberculosis of serous membranes 
can in some cases only be made out by the detection of friction 
sounds or by palpation of the peritoneum through the rectum ; it 
may exist extensively without the occurrence of any emaciation of 
the animal (so-called "fat Frenchmen"), but on the contrary with 
preservation of an excellent state of nutrition. In the same way 
involvement of the deeper lymph glands, liver and intestine is apt 
to escape diagnosis during life. 

Diagnosis can be positively confirmed by the microscopic exam- 
ination of the various emanations (milk, vaginal discharge, bron- 
chial mucus, etc.) by determination of the tubercle bacilli therein. 

As a valuable aid to diagnosis especially in the latent forms of 
the disease, the use of tuberculin may be approved ; this is a decoc- 
tion of cultures of the tubercle bacillus [sterilized by filtration 
through porcelain] which has the effect of causing a- febrile 
reaction in tuberculous subjects, non-tuberculous individuals, how- 
ever, manifesting no reaction to similar doses of the material. 



Glanders. 311 

Tuberculosis can be successfully combated as purely conta- 
gious-infectious disease by regulations contemplating required dis- 
infection of all effluvia containing tubercle bacilli. Recently a 
method of protective inoculation of cattle against tuberculosis has 
been discovered by v. Behring, immunizing the animals by means 
of strains of tubercle bacilli of low virulence. [Dixon in 1889 
found that he obtained resistance in rabbits against virulent bovine 
bacilli after having previously inoculated them with material from 
an old laboratory culture containing club-shaped and branching 
forms. It is of interest, too, that successful vaccination of cattle 
against virulent bovine tuberculosis has been practiced by Pearson 
in this country, using cultures of human tubercle bacilli of low 
virulence.] Cows which have obtained a high degree of immuniza- 
tion produce milk which possesses a certain amount of immunizing 
bodies ; and it may be hoped that either by using such milk or the 
serum of highly immunized animals there may be obtained also a 
curative method for consumption in man. 

Glanders. 

Glanders (malleosis) is a contagious disease caused by the glan- 
ders bacillus (bacillus mallei), occurring in the horse, ass and mule, 
but very infectious and dangerous to man and also transmissible to 
carnivora, sheep, goat, guinea-pig, hedge-hog, field-mouse, rabbit 
and camel. The cow is entirely immune even after every effort at 
inoculation ; and the hog can be infected only with considerable dif- 
ficulty; domestic fowls are also immune. 

This infectious malady causes both in its acute and chronic course 
(the latter perhaps persisting for years) a purulent fibroplastic in- 
flammatory change, developing mainly in the skin and respiratory 
mucous membranes. Pathological changes also invariably occur in 
the lymph vessels and lymphatic glands ; and in addition metastatic 
foci may follow in the spleen, liver, testicles, kidneys, sometimes in 
the flesh, and finally a general blood infection results. 

The microorganism of the disease, the glanders bacillus, discov- 
ered by Schiitz and Loeffler, is always present in all tissues the seat 
of glanders changes, in the discharges of the subject mixed with 
glanders pus, and is sometimes found in the blood. It is a short rod- 
shaped organism, measuring from two to five micromillimeters in 
length and from one-half to one micromillimeter in width. It does 
not exist free in nature, but multiplies exclusively in the animal 
body (cf. contagious diseases, p. 71) ; only under special conditions 



312 Specific Inflammations. 

can it be grown* in the incubator on nutrient media (glycerine 
bouillon, serum, agar, potatoes). 

Transmission of the infectious agents from one animal to an- 
other or to man is the result of a close relationship (living together) 
or actual contact of the diseased animals with others ; and may take 
place when the vehicle of the contagion (pus, nasal discharge, etc.) 
gets upon the fodder and in the water, or when discharged in cough- 
ing or blown out in sprays of fine drop- 
ft f* lets and inhaled by other animals. If 

I f ( the material should lodge on the skin 

\ %"\/ \ and mucous membranes it may pene- 

&yjf \ trate even through apparently intact 

** * pores (transmission by blankets, saddles 

£ v « and harness soiled with the pus). Ar- 

1 tificially the disease may be reproduced 

\ * ?J& bv cutaneous, subcutaneous, intraperi- 

' ™ ** ~ v toneal and other forms of inoculation, 

Fig 73 and by feeding the glanders germs to 

Glanders bacilli (from cui- the susceptible animals. From the ex- 
perimental studies of Nocard and 
Leclainche, Galtier, Conte, Renault, Cadear and Malet, the 
smallest lesion of the epithelium in mucous membranes 
may serve as a point of entrance for the germ, as the trivial lesion 
which is produced by rubbing with a piece of linen cloth or the 
tiny epithelial abrasions about the nostrils caused by bits of food- 
stuff. In guinea-pigs the infection may be successfully produced by 
dropping the glanders bacilli into the conjunctival sac upon the in- 
tact mucous surface, probably through the lymph follicles and tear 
ducts. In feeding experiments the lymph-follicles of the pharnyx 
and intestine are the points of entrance of the infection. Inhala- 
tion of the germs distributed by spraying also occasions infection of 
the pharyngeal mucous membrane. The infection develops most 
rapidly after intravenous and intracranial injection. 

The bacilli multiply at first locally upon and within the tissue 
(lymph spaces, lymph follicles) to which they have gained access, 
and produce by the influence of their metabolic products a progres- 
sive cellular necrosis with destruction of the nuclei (formation of 
granules and globules, fragmentation of chromatin) and trans- 
formation of the cells into finely granular detritus. Coincidently 
there is seen a continual emigration of the white blood corpuscles, 

* For details cf. Kitt. Bakterienkunde fur Tierdrzte. IV AufL, Wien., 1903. 



Glanders. 



313 



that is, a local inflammation, which in the chronic form of the affec- 
tion also produces a wall of demarcation by fibroblasts. With 
the persistent and progressive multiplication of the bacilli in the 




Fig. 74. 
Microscopic section through a glanders nodule in lung of horse. 




Fig. 75. 
Glanders nodules, erosions and ulcers of the nasal septum of horse. 

inflamed and necrobiotic tissue, this limiting new tissue is, how over, 
continually being broken down and the area of destruction is 
widened. The virus being taken up by the leucocytes, multiplying 



314 



Specific Inflammations. 










■^flfflBg 



r 



in the lymph spaces and therefore open to lymph convection, is dis- 
seminated in the vicinity of the primary focus, passes along the 
lymph vessels and into the blood ; and new points of deposition and 
new foci of the disease occur locally and metastatically. The bacilli 
are also carried by currents of secretion and may lodge in a freshi 
position on the mucous membrane, here again to give rise to new 
colonies, as where they are carried from the lungs to the larynx 

and pharynx. The metabolic prod- 
ucts of the organisms, developing in 
the system, by their toxic influences 
occasion fever and wasting. 

The visible anatomical changes 
of the disease vary considerably with 
the virulence of the affection and the 
tissue predisposition of the particu- 
lar kind of animal. The principal 
types are the glanders nodules, 
glanders abscesses, glanders indu- 
rations and glanders infiltrations. 

Glanders nodules } developing 
mainly in the lungs and parenchyma- 
tous organs, appear as grayish-white, 
semitransparent, opalescent, rounded 
prominences or deposits ranging from 
the size of a grain of sand to that 
of a pea, their central portion break- 
ing down into a yellowish-gray, 
purulent or dry cheesy material. In 
the lung the}* are often surrounded 
by a dark red area. The glanders 
ulcers present themselves on the mu- 
cous membranes of the respiratory 
tract as shallow or deep lesions, varying from the size of a lentil 
to that of a silver dollar ; the loss of substance giving the mucous 
membrane an appearance of being eaten or gnawed. The larger 
ones have thick, wall-like, eroded margins. These ulcers have a 
bacon-like gray color, with the bordering mucous membrane often 
dark red and hypersemic, bleeding on the least provocation. There 
are usually large numbers upon an affected mucous membrane. 
The glanders ulcers of the skin range from the size of a lentil to 
that of a half dollar, are of a dirty grayish-red color, covered with 




Fig. 76. 

Glanders induration of the nasal 

mucous membrane of the 

horse. 



Glanders. 315 

pus and half dried crusts, and the surrounding hairs are soiled with 
pus. These ulcers often undermine the skin producing crater-like 
openings (like the anus of a chicken) and are apt to be found in 
rows one after another and alongside of each other. 

Glanders abscesses are commonly found in the skin as some- 
what rounded boils of the size of a hazel nut or a walnut, with the 
hair lost from over their surface. They fluctuate and contain a 
thin, oily, yellow or yellowish-red pus, sometimes a rather thick and 
mushy detritus, and their Avail is made up of bacony, eroded cutis 




Fig. 77. 
Glanders nodules and indurations of lung of horse. Natural size. 

and induration tissue. They are apt to be found in rows enclosed 
in the swollen, dense lymphatic cords ; that is they form foci of sup- 
puration interrupting the lymph vessels like a rosary. 

"Glanders indurations occur on mucous membranes as the result 
of a demarcating fibroplastic proliferation in the form of solid, nod- 
ular or ridge-like, thick prominences of the mucous membrane, with 
a yellowish-gray to reddish-yellow color, and a smooth slippery sur- 
face. These thickenings may appear as isolated prominences of the 
size of a hemp seed or oat seed, or may be U\^\\ so as to form hard 
stellate and radiating scars like frost-crystals, not extending deeply, 



3i6 



Specific Inflammations. 



and projecting somewhat above the surface. They are scattered all 
over the surface of the mucous membrane, often in large numbers, 
and may sometimes occur in rows. Sometimes this chronic indura- 
tive inflammation may form patches of thickening- a finger's length 
in extent and several centimeters broad, standing out like cushions 
in marked relief, sometimes of dull grayish-yellow color or mottled 
with bright red points, and their smooth surface covered with a 
viscid pus. Occasionally warty, soft, raspberry-colored, projecting 
granulations are found growing from the mucous membranes. 
In the lungs indurative patches are met sometimes about suppu- 




Fig. 78. * 

Glanders abscesses of the skin of horse. (Photographed by Dr. Jakob.) 



rating and caseating glanders nodules as bacony, grayish-white 
zones of demarcating tissue, sending radiations into the pulmo- 
nary tissue ; sometimes as broad yellowish-white, poorly defined 
areas of connective tissue, merging into the pulmonary structure, 
involving numerous lobules and changing them into a dense mass, 
and cutting with a tough, leathery resistance. On the inside of such 
areas are met dull yellow, ochre-colored, moist cheesy or dry 
plaster-like deposits. 

Glanders infiltrations develop in the lung as true pneumonias of 
catarrhal, suppurative or croupous types, and as a sclerosing form; 
the former in acute, the latter in chronic glanders. Especially in 



Glanders. 



317 



the cat family the lungs are involved just as in croupous pneumonia 
and show stages of red and gray hepatization. In the horse the 
lungs are apt to show a confused mixture of inflammatory changes ; 
groups of lobules are found all through the lungs forming wedge- 
shaped, swollen areas of a densely elastic consistence cutting like 
bacon, mottled reddish-yellow or grayish-yellow and leaving on, the 
knife blade a turbid muco-purulent juice. In the chronic type the 
pulmonary tissue is changed into an extremely tough, light grayish- 
yellow mass of connective tissue riddled with confluent cavities about 
as large as a thumb's breadth, filled with a slimy, oily pus and having 
a deeply reddened inner surface. In this type of change the lymph 




Fig 79. 
Large glanders ulcer of nasal septum of horse. 



glands become very large and swollen, soft like marrow ; afterwards 
densely indurated and changed into a tough white connective tissue, 
forming nodular bunches as large as a goose tgg which become ad- 
herent to the surrounding structures by similar fibrous bands. In 
the interior of these hyperplastic and inflamed lymph glands is 
encountered either a purulent softening in isolated spots or exten- 
sive purulent liquefaction with cavity formation, or an indurated, 
dry cheesy necrotic focus. The multiplication of the glanders 
bacilli in the lymph paths, besides causing them to swell up like 
cords, also gives rise to a diffuse gelatinous infiltration (especially 
because of the lymph stagnation), and, if the inflammation become 
chronic, to broad connective tissue thickenings ; so that, for example, 
the loose cellular tissue of the skin becomes the seat of gelatinous 
thickening with extensive indurations all through it (pachydermia, 
elephantiasis) with foci of suppurative necrotic destruction running 
all through the skin and subcutaneous tissue. 



318 Specific Inflammations. 

These more important anatomical changes of glanders are met 
associated with each other and succeeding one another ; so that 
along with the pneumonic infiltration of the pulmonary lobules 
glanders nodules are apt to be met in the same case; along with 
the abscesses, ulcers also are encountered, the latter developing 
from the former, and the diffuse infiltrations occurring as a 
terminal change. 

Glanders generally may be considered as an irrecoverable infec- 
tious disease; exceptions have been met occasionally in man, guinea- 
pigs and horses, but are so rare that attempts to cure are hardly 
worth the effort in the case of animals, and seem to be injudicious, 
when the daily danger is considered of the transmission of the in- 
fection to man and other animals from the subjects dragging out 
the course of their disease for months and years. The only rational 
method of exterminating the disease consists in killing the animals 
and carefully doing away with every chance of harm from any ani j 
mal known to be afflicted with glanders ; and these provisions should 
be made binding by law. 

For details concerning the aetiology, symptoms and prophylaxis, refer- 
ence may be made to Friedberger and Frohner, Veterinary Pathology, 
Amer. Ed., W. T. Keener & Co., Chicago, 1904; Nocard-Leclainche, Les 
maladies microbiennes des animaux. Ill edition, Paris, 1903. 

Actinomycosis. 

Actinomycosis (d/cr/s , ray ; ^ktjs, fungus), or Ray-fungus Disease, 
is a form of wound infection manifesting itself by the anatomical 
changes of a suppurating granulomatous inflammation ; it may be 
caused by several varieties of a group of fungi known as the ray 
fungi or actinomycetes. It occurs not infrequently in man, cattle 
and swine and has been exceptionally observed also in sheep, hart 
and roe deer, dogs, cats and elephants. 

The fungi which cause the affection were first discovered by 
Langenbeck in 1845 * n the carious lumbar vertebrae of a man, later 
by Rivolta in 1868 in tumors of the jaw in cattle and by C. Hahn 
in 1870 in the tongue in cattle ; and have been more fully investigated 
by Bollinger, Harz, Johne, Israel, Ponfick, Gasperini, Berestnew, 
Bostrom and others. They have wide distribution in nature, existing 
especially in field soil and the beards of cereals. The usual mode 
of infection by the ray fungi is through wounds made by small for- 
eign bodies penetrating into the skin or mucous membranes, as sharp 



Actinomycosis. 



3*9 



spicules of grain or other stiff particles of food to which the fungi 
are adherent; or they may gain access to the tissues through 
scratches and similar lesions of the skin. Examples of such mode 
of infection are common. Persons who put heads of grain into their 
mouths or who accidentally swallow portions of such heads or who 
have been injured while harvesting, have been known to develop 
at the points of injury (gums, throat, hands) actinomycotic ab- 
scesses and growths. Swine pastured in stubble land where their 
teats are easily wounded by the stiff straw stubble are not infre- 



Zungen b asis 



Rachen/vand 



Actcno 
mucom 




Fig. 80. 

Fungous actinomycosis in pharynx of cow. Actinomycom, actinomycotic tumor. 
Rachertwandj wall of pharynx. Zungenbasis, base of tongue. 



quently known to develop actinomycosis of a mammary gland. 
Cattle frequently show actinomycosis of the tongue, gums or lips 
along with the presence in the tissues of spicules of grain or other 
food materials which have been forcibly lodged in between the teeth, 
in the pharynx, etc. Occasionally in castration the fungi from the 
straw of the bedding get into the operation wound and set up acti- 
nomycosis of the stump of the seminal cord and scrotum (for de- 
tails cf. Schlegel and Kitt*). The occurrence of actinomycosis oc- 
casioned in some such accidental way (pasturing in stubble fields) 

*ii<in<iu. dcr pathog. Mikroorg., v. Kolle and Wassermann; Gustav Fischer, 
Jena, 1903. Kin Bacterienleunde fUr Tierarzte, iv Ami. Wten., 1903, 



320 Specific Inflammations. 

has more frequently been observed than an actual epidemic affection 
(Bang, C. O. Jensen, Preusse). 

Transmission of actinomycosis from one animal to another or to 
man is very improbable ; the few alleged cases of such an occurrence 
which have been recorded in literature might equally well have been 
caused by traumatic infection. Artificial transmission by inocula- 
tion has been successful only in a few cases (Johne, Wolff and Is- 
rael, Ponfick and others), and in these the experiment animal had 
to receive rather deep inoculation with comparatively large amounts 
of the infectious material (intraperitoneal, subcutaneous injection); 
while in ordinary wound infection and feeding transmission failed 
completely. 

The anatomical changes brought about by the actinomycotic in- 
fection include the formation of actinomycotic nodules, abscesses 
and fungous granulomatous proliferations, sometimes accompanied 
by indurative connective tissue proliferations. 

The actinomycotic nodules (actinomycosis nodularis) are small 
inflammatory foci of the size of a millet seed to that of a pea, yellow- 
ish-red or grayish-yellow in color, composed of a soft granulation 
tissue, which is developed as the product of a demarcating inflam- 
mation about the fungus which acts as a foreign body. They show 
one or a number of opaque yellow punctiform spots from the pres- 
ence in minute foci within them of the yellow colored clumps of 
fungi and pus cells. When they are in the parenchyma of an organ 

they are surrounded by a connective tissue 
■**wzrr, df&Hu. zone of induration ; when on mucous surfaces 

^Mi^M^MmM, they break through and project somewhat. 

Actinomycotic abscesses (actinomycosis 
purulenta, apostematosa) are areas of soften- 
ing from the size of a plum stone to that of a 
Flg ' 81 " human head, with purulent content which 

Actinomycotic clump. . 

(After Ostertag.) either appears as a trim mushy fluid, creamy 

and of a sulphur yellow color, enclosed in a 
white indurated abscess wall, or the areas are made up of a flabby, 
grayish-yellow to reddish-yellow matrix, which contains the infil- 
trating pus, not in separate foci large enough to allow it to be taken 
out in a spoon, but just as though it were in a fine sponge. In the 
latter case there is no real abscess membrane present, although the 
surrounding tissue for some distance is converted into an indurated, 
dense white connective tissue. 

The fungous actinomycotic growths (actinomycosis fungosa) 
look like mushrooms or soft cushions, projecting above the surface 




Actinomycosis. 



321 



of the skin or mucous membrane. They are more or less peduncu- 
lated growths, varying in size from that of a nut to that of a fist, 
covered with blood and pus and crusts, with an elastic, soft consist- 
ence, on section looking like bacon, grayish-white or grayish-red, 
and thickly beset with points of suppuration or the described flabby 
yellow patches of softening. 



- a 




A* 




. <?Vo *r&% '*%,*. 



TAI 



Fig. 82. 



Nodule of actinomycosis (high magnification) : a, fibroblastic and epithelioid bor- 
der ; b, leucocytic central portion ; v, actinomyees. 



All three of these forms may occur together and pass into each 
other. For example, after rupture of an abscess the granulomatous 
proliferation springs up and grows out as a fungous mass ; or the 
small nodules, because of the progressive multiplication of the fungi, 
become confluent and form the larger flabby areas of softening ; or 
the bacon-like connective tissue growth prevails, and this causes 
more or less marked induration of the organ. 

The most characteristic thing about the actinomycotic growth is 
the fungus. This may be recognized even by the unaided eye as 
minute granules the size of a sand grain, soft like tallow or some- 
times of a chalky consistence, of a sulphur-yellow color or white ; 



$22 



Specific Inflammations. 



they may often be present in large numbers in the softened areas 
and the pus from this may sometimes have an almost sand-like, gritty 
consistence. Under the microscope the fungi may be discerned in 




Fig. 83. 
Head of cow with actinomycosis of jaw. (After Moussu.) 

unstained preparations as strongly refractive, gray or shining-yellow 
clumps of club-shaped filaments arranged in the form of a rosette 
(fungus glands) ; in stained sections the filamentous, intricately 




T 



Fig. 84. 
Actinomycosis of the nasal mucous membrane of cow. 



branched mycelium forming the matrix may be seen, and the 
clump, with its budding elements swollen into club shape and 
growing out from the periphery in radiating fashion.* The 

* For fuller description c"£ Kitt, BakterienJcunde f. Ticrdrife, IV Aufl., Wien, 
M. Perles Verl 1903. 



Actinomycosis. 323 

clumps of fungi are always surrounded by leucocytes in the fatty 
and granular detritus, sometimes, too, with here and there a giant 
cell. About this central, softened focus proliferating fibroplastic 
tissue is formed, vascular and full of emigrated leucocytes, as a 
zone of varying width. 

Actinomycosis is primarily a local affection, running a course of 
months or years in duration. As the fungi penetrate the lymph 
spaces and are carried to new positions fresh eruptions in multiple 
foci of inflammation along the lymph vessels and in the lymph glands 
arise, with purulent softening and coincident production of new 
tissue in the soft parts and in the bones. By haemic convection 
also the process may become a general one, a number of organs, 
bones, etc., becoming synchronously or one after another involved. 
[In cattle one of the most common and characteristic results of 
actinomycotic infection is that seen in involvement of the jaw, 
which may well illustrate many of the features of the disease. The 
infection here is supposed to take place by the penetration of a 
small spicule of grass or beard of grain into the gum along 
the root of the tooth, such a foreign element having upon it 
the actinomycotic fungus. In unknown way the fungus penetrates 
along the root well into the alveolar process of the jaw, and there 
produces the small nodules above described, each undergoing cen- 
tral softening and disintegration, and being surrounded by a zone 
of new tissue formation at its periphery. Gradually the process 
loosens the teeth ; and as they are elevated in their sockets by the 
inflammatory tissue, and chewing becomes painful, the animal 
stops eating. Sometimes the teeth are forced up so that the animal 
is unable to close the mouth without pain, and the teeth may even 
be lost. The process gradually spreads throughout the alveolar 
bone and into and through the whole thickness of the jaw, the in- 
flammatory change about each nodule at first causing absorbtion 
of the calcareous matter, and thus giving the fungi a chance to 
spread in thi's softened tissue. As each nodule grows older, the 
formative tissue at its periphery produces new bone ; and from the 
coincident operation of the two factors of bone destruction and 
bone formation the jaw becomes enormously enlarged ("big-jaw"), 
riddled with the small points of softening representing the different 
actinomycotic foci and with fistulous paths running all through the 
mass, connecting these points of disintegration. The jaw may thus 
have developed within and upon it a tumor-like mass the size of a 
double fist or much larger, composed of a coarse framework of 



324 Specific Inflammations. 

newly formed bone like a coarse calcareous sponge, the meshes of 
which are occupied by the actinomycotic nodules and their purulent 
matter. Fistulous sinuses discharge upon the surface and into the 
mouth ; and in the purulent material are to be seen the tiny yellow 
sand-like grains known as "sulphur grains," consisting of the fungi 
themselves. The animal may die from starvation ; the process may 
extend along the ramus of the jaw to the base of the skull and 
gradually advance by the same changes through the latter and cause 
death from a purulent meningitis ; or the fungi may be carried 
along the lymphatics of the neck to the thorax, producing an acti- 
nomycotic pleurisy and entering the lung to cause fibrosis and puru- 
lent destruction of these organs. Occasionally the fungi swallowed 
with the discharge into the mouth give rise to alimentary actino- 
mycotic . abscesses.] 

Lignieres and Spitz have described an epidemic disease of cattle 
similar to actinomycosis occurring in Argentina, in which the skin and 
lymph glands are principally involved (rarely the bones of the face and 
tongue). The yellow fungus grains are not present, and another species of 
microphyte which does not stain by Gram's method is regarded as the 
cause (actinobacillosis). 

Botryomycosis. 

By the term botryomycosis is meant a productive inflamma- 
tion which leads to the formation of fibrous growths or cicatri- 
cial indurations attended invariably with suppuration and fistula 
formation or the production of brownish to yellowish-red foci of 
softening, and which are caused by infection with botryomyces 
ascoformans. The disease is quite common in the horse; and 
has been met a very few times also in the cow and hog (Csokor, 
Wilbrandt). 

The fungus which is the productive agent of the disease, dis- 
covered independently by Bollinger in 1870, Rivolta and Micel- 
lone in 1879, an d by Rabe and Johne, presents itself in the dis- 
eased tissue as a deposit of fine sand-like granules, visible to the 
naked eye. Microscopically it is characterized by the occurrence 
of the fungi in blackberry-like masses (fifty to one hundred 
micromillimeters in size) made up of conglomerated round, disc- 
like masses of cocci grouped together in zooglceae.* 

This fungus gains entrance to the tissue by infection of 
wounds ; apparently it may find its way through small excoria- 

* For fuller description cf. Kitt, Bakterienkunde fiir Tierargte. IV Aufl., 
Wien, 1903, 




Botryomycosis Tumors. 325 

tions in the epiderm or through the glands of the skin, as botryo- 
mycotic growths develop especially at places in the skin which 
are frequently subject to friction (places worn by harness and 
saddle.) Very frequently the growth involves the stump of the 
spermatic cord after castration, or the udder and penis sheath, as 
well as the bursae and fasciae of the withers, elbow and shoul- 
der. The tissue invaded by these microorganisms becomes the 
seat of a chronic inflammation. At first it has a grayish-red color, 
later becoming pale and translucent (like 
bacon) ; and eventually a white cicatricial 
connective tissue develops in the mass, 
spreading through the loose cellular tissue 
and over the surfaces of the fasciae and 
producing enormous induration and thick- 
ening of the part. Or the process may 
be more definitely limited to spheroidal 
nodular masses which project from the sur- 
face as fibroma-like tumors, ranging in size Fi s- 85 - 
from that of a fist to that of a human head Botryo ^ S poweJ)!' manS 
or larger. The growth of the clumps of 

microorganisms in this fibroplastic tissue brings about foci of 
softening of a viscid purulent type, sometimes of a distinct yel- 
low color like ordinary pus, but commonly of a saffron or 
orange tint, with formation of fistulse to the surface and paths of 
confluence in the mass. As the result of multiple coincident or 
successive infection of the skin there often are met dozens of these 
botryomycomata in one subject. Convection of the microbic agents 
by the lymph and blood leads to metastatic growths, especially in 
the lungs. 

For fuller account cf. Kitt, Spezielle pathol. Anatomic der Hauliers, 
II. Aufl. F. Enke, Stuttgart, 1901. 

New Growths, Tumors, Autoblastomata. 

By the terms new growths, tumors, new formations, neo- 
plasms, autoblastomata (Klebs), are meant tissue proliferations 
of persistently progressive character, which alter the conforma- 
tion of the part and disturb its function. These growths appear 
as excessive tissue accumulations caused by cells of the animal 
body which have become parasitic in nature and which invade 
the soft structures or skeleton of the animal as more or less 
isolated and independent bodies. Enlarging sometimes slowly, 



326 Tumors. 

sometimes rapidly, and never undergoing diminution, they inter- 
fere with the other tissues, perhaps by robbing them of their 

nutrition, perhaps by some of the products of their metabolic 
changes, but particularly in a mechanical way by their pressure 
influences. 

It has been only within the last sixty years, since Rudolf 
Virchow by comprehensive histological studies and critical 
examination of the older literature established a new basis for 
the systematic consideration of the different types of tumors, 
that a scientific conception of the origin and nature of new 
growths has entered into their study {oncology; 6 87*05, node). 
Previous to this period tumors were classified mainly from their 
external appearances and their gross anatomical characteristics, 
and were named frequently from incidental features often of 
merely accidental prominence ; and no real knowledge was had 
of the developmental history of these growths. Although in 
our present knowledge of the development of tumors there are 
many missing links, we nevertheless possess from microscopic 
and experimental investigations sufficient information in regard 
to their nature to permit us to clearly recognize their derivation 
from the cells of the body, the mode of their extension and their 
actual method of growth, and the significance of the pathological 
process in its bearing upon the life of the subject. 

Tumors may te classified from their histogenesis, that is. 
from their structure and from their origin and construction from 
the cells and tissues of the body. There are no foreign tumor ele- 
ments brought into the body from without ; tumors are offsprings 
of the bodv cells, and are according- found to consist of these 
and of the intercellular substances of the various tissues. They 
develop according to the same laws which govern the embryonic 
development and later growth of the individual and the processes 
of regeneration : and they arise from the four primary types of 
body tissue ('connective tissue in all its forms, epithelium, muscle 
and nervous tissue.) 

Just as the tumor cells present the same form and the same 
mode of multiplication as the mother cells from which they are 
derived, the intercellular substances, as products of the cells, are 
the same as are produced by the original cells. Generally, there- 
fore, the source of a tumor can be determined from the character 
of its tissue : although because of the fact that they grow more 
or less independently, as isolated masses of tissue, it is quite 
reasonable to expect more or less modifications in the structure 



Classification of Tumors. 327 

and adaptation of the cells and matrix of tumors. The cells 
frequently do not attain the same size as the mother cells or 
may be larger than the latter ; cellular division takes place some- 
times as a direct process, sometimes indirectly with mitotic 
changes. The mitotic figures, which are likely to be found in 
great numbers, especially in rapidly growing tumors, and the 
process of cellular division often show irregularities pointing to 
a pathological disturbance of the process. . The chromatin fila- 
ments derived from the chromatin skein (chromatosomes) may 
be too numerous or asymmetrical ; or there may be found giant 
mitoses, karyokinetic figures in multipolar arrangement, arranged 
about a number of attraction centres (centrosomes), or giant 
cells. The cells may also, as stated by Ribbert, exhibit altera- 
tions which may be regarded as regressive in character, as a 
return to an embryonic state in which there is but little evidence of 
differentiation ; or they may really be embryonic cells whose 
power of forming normally functionating organs has been lost 
(a change designated by Hansemann by the term Anaplasia) . 

The cellular type and the character of the tissue of the growth 
furnish the basis for nomenclature of tumors. Many tumors are 
made up of but a single kind of tissue, as fibrous connective 
tissue, fat tissue or cartilage, or at least mainly of one type (the 
accompanying bloodvessels are not regarded as a special form of 
tissue but as essential constituents of any form) ; such growths 
are called simple autoblastomata. Others, no less numerous, 
contain two or more tissues, as is obviously required in epithelial 
new growths because epithelium always requires a connective 
tissue substructure, and as is likely to occur, too, in other tumors 
from the mixture of the various forms of connective tissue, as 
cartilage, bone or fat; we therefore recognize as a second group, 
the compound autoblastomata or mixed tumors. 

It should be recognized, too, that tumors as independent devel- 
opments, although relying on the animal body for their nutri- 
tion, yet having their own blood vessels and carrying on a 
separate metabolism, are subject to all the pathological processes 
which may affect the normal tissues of the body. A tumor may 
become the seat of passive hyperemia, of inflammatory reaction ; 
and any kind of degeneration and necrosis may occur in the 
tumor structure. Tumors are sometimes subject to traumatic 
influences from without (strangulation, wrenching, penetration 
by foreign bodies or bacteria) which may occasion tissue 
changes ; sometimes the conditions of nutrition become so un- 



328 Tumors. 

favorable from irregularities of growth of the individual con- 
stituents of the tumor (as the imperfect development of blood 
vessels) or from the absence of ducts for the escape of secre- 
tions, or from the retention of metabolic products, that regres- 
sive metamorphoses, as fatty degeneration, calcification, mucoid 
degeneration, etc., necessarily take place. When such condi- 
tions prevail and when the structure of the growth is modified by 
this or that change there is often considerable difficulty in deter- 
mining the derivation of the tumor and there may be much un- 
certainty under which group of tumors a given neoplasm should 
be classed. In such cases we follow the proverb: a potion fiat 
denominatio ; and the anatomical term is given from the pre- 
dominating type of tissue present. 

Growth of Tumors. — Derived from one or more tissues, tumors 
at first form cellular masses (or a tissue complex). These in- 
crease in size as the internal portions of the new formation 
multiply, that is, by central growth; or they enlarge by progres- 
sive multiplication of the outer portions, that is, by peripheral 
or oppositional growth. The increase in size and extension of 
the tumor therefore may take place by one or other of two ways ; 
either by the tumor growing "as a bulb, lying in the soil and 
developing, presses aside the ground'' (Durk), "as a rubber bal- 
loon which one inflates'' (Ribbert) (expansile growth), or by 
the tumor tissue sending out processes into the neighboring struc- 
tures as a plant forces its roots into the earth (infiltration growth). 
It was formerly believed that the enlargement took place by the 
surrounding tissues becoming gradually involved in the same 
proliferative process, being actually infected (local infection) ; but 
this is not probable, as we may usually recognize under the micro- 
scope that the proliferating cells of the neoplastic primary focus, 
that is, the first elements of the tumor, are extending into the 
surrounding tissue, growing into the interior of the tissue or 
toward the surface of the part. The surrounding tissue supplies 
only the nutrition for growth and takes part only in this sense 
that its blood vessels and supporting tissue may be appropriated 
by the new growth, and that it may also multiply as the result 
of the changes in tissue tension which may be produced (v. 
chapter on Regeneration) ; otherwise, however, the surrounding 
tissue plays but a passive part, like the soil in relation to the 
seed of grain. 

External Shape of Tumors. — In correspondence with their 
mode of growth autoblastomata form usually circumscribed 



Tumor Shapes; Significance of- Tumors. 329 

tumors well defined from the normal tissues. They may develop 
as nodes (tuberous growths) which lie embedded in the tissue 
like the yolk within an egg, or may protrude as tuberosities ; they 
may grow out from the surface of an organ as pedunculated 
protuberances, with thick pedicle like a mushroom {fungous form), 
or with slender pedicle and provided with free offshoots like a 
polyp with its tentacles {polypous shape), or like a tree {den- 
tritic), like a coral stalk or like cauliflower; or, in the infiltrating 
varieties they may occasion a uniform swellmg of the affected 
organ. [Any tumor growing from a surface and provided with a 
slender pedicle may be spoken of as a polyp or a polypoid 
growth, whether branched or smooth. A form known as a flat 
tabular swelling is often encountered where upon a surface the 
growth has produced a more or less uniform swelling with a 
flattened surface, as is often seen where the surface of a growth 
is opposed by a second surface causing pressure. The causes 
determining the various shapes of tumors include such factors as 
the mode of growth (central growth producing a regular ap- 
pearance of the periphery, while infiltrative growths are apt to 
be irregular and ragged in outline), pressure, (as just suggested 
in connection with the flat tabular swelling, or the preservation of 
the spheroidal shape of 'a node by the pressure from all sides by 
the surrounding tissues, or where an analogous growth appears 
as a tuberosity or polyp if developing close to a surface, being thus 
relieved of pressure on the surface side), and the original structure 
from which the tumor arises (as where a. surface growth, a 
papilloma, takes on a villous type of branching following the 
natural formation of villi from the original tissue, as in the 
intestine.)] 

The Pathological Significance of Tumors is determined pri- 
marily by their location, their size and the mechanical pressure 
which they exert upon the adjacent tissues. By pressure upon 
the peripheral tissues a tumor as it grows in size occasions some- 
times trifling and at other times serious disturbance of func- 
tion, varying with the particular organ affected. A small 
tumor in the brain or in the cranial cavity may by compression 
of the former or of the cerebral vessels bring about most intense 
nervous troubles and terminate fatally ; and by obstructing the 
larynx, gullet or intestinal canal a comparatively small growth may 
endanger life. Pressure upon bloodvessels may occasion a great 
variety of circulatory disturbances. But, on the other hand, even 



330 Tumors. 

large growths of the skin or subcutaneous tissue often produce 
only the most trifling effects. 

In the second place the pathological significance depends 
upon the degree of special power which the tumor possesses to 
disseminate through the system. The less a tumor involves 
strictly the surface of an organ or the less it remains closely 
confined to its point of origin as a single isolated growth, and 
the more it sends out offshoots which extend into the lymph- 
passages and bloodvessels and thus obtains opportunity for its 
cells to be loosened and carried into new locations in the body, 
the more the development of the neoplasm acquires specially 
dangerous characteristics. The outshoots of a tumor, made up of 
its proliferating cells, force their way first in the surrounding tis- 
sue, especially the connective tissue lymph spaces, which repre- 
sent the beginnings of the lymph passages, causing a continually 
increasing portion of the organ in which the growth occurs to be 
destroyed by the infiltration (the tumor therefore spoken of as a 
destructive growth or locally penetrating growth). In such new 
formations the external, visible outlines are usually not its actual 
limits; the apparently healthy adjacent, tissue may conceal the 
roots of the tumor only to be found microscopically. The sur- 
geon, whose skill can in many cases afford permanent recovery 
by removal of the growth, is unable occasionally (for technical 
reasons or because the precise limits of the individual roots 
cannot be recognized by the unaided eye) to remove the entire 
tumor in the operation performed for its ablation ; from the 
portions thus left, earlier or later the same tumor may return in 
the original site or close by {recurrence of tumor). The tumor 
cells grow into the lymph passages, sometimes as continuous 
cords or roots ; or the cells may become loosened or be carried 
away by the lymph current or perhaps by leucocytes. The 
same thing occurs where the roots of the tumor penetrate through 
the wall of a blood vessel, sometimes developing as long pro- 
cesses within its lumen ; and particles of the growth may be 
swept off by the blood current. Under such circumstances, at a 
shorter or longer distance from the (primary) autoblastoma (the 
principal tumor) arise secondary tumors, daughter tumors or 
metastatic tumors. The lymphogenous metastases are carried 
into the immediately adjacent tissues and into the lymphatic 
glands draining the site of the original growth ; the embolic 
(hematogenous) ones pass into the lungs or the organs of 
the greater circulation (v. chapter on Embolism). When in this 



Pathological Significance of Tumors. 331 

manner the tumor is disseminated widely to the various organs, 
we speak of the generalization of the tumor. This lodgment and 
development of daughter nodules from the cells which have be- 
come freed from a tumor, an actual form of seeding by trans- 
plantation, is met also at contact points on mucous and serous 
surfaces. For example, an ovarian tumor may become dissem- 
inated all over the peritoneum by having its cells loosened and 
scattered over the serous membrane ; a tumor of the costal pleura 
may become transplanted to the visceral pleura ; one of the 
upper lip to the lower lip. The cellular elements of the growth 
in such instances are freed and distributed by the movements of 
the viscera, or by the friction of contiguous surfaces. 

All secondary growths correspond closely with the primary 
tumor from which they arose in their histological structure ; 
where a cancer of the gum metastasizes to the retropharyngeal 
lymph glands and lungs the metastatic formations are composed 
of squamous epithelial cells just as is the primary tumor. They 
need not necessarily be smaller than the original growth, and 
are often of larger size than the latter. 

Tumors which can be completely removed, which are not metastatic 
and do not recur, are ordinarily called, from the clinical point of view, 
benign (innocent) ; those which penetrate into the adjacent tissues and are 
removed in their entirety with difficulty, or are recurrent and give rise 
to metastases, are called malignant (harmful). To the extent that experi- 
ence shows that one or other of these results may generally be expected 
in operations for removal, the classification into these two types may be 
accepted ; but the differences are not to be depended upon, as some tumors 
which do not form metastases recur if not completely removed, and 
tumors which are ordinarily regarded as benign may occasionally produce 
metastases ; and, again, well-known malignant growths often remain strictly 
localized and harmless for a long time, and if they are removed early 
enough will not recur. 

As a further factor by which tumors may affect the system, 
it should be recalled that within these neoplasms all sorts of 
metabolic products and decomposition substances are being freed, 
and these may by absorption have toxic influences upon the 
possessor of the growth. It is quite common to meet with in- 
flammatory changes in the tissue about a tumor and the growth 
itself may be found richly infiltrated with immigrating leucocytes, 
or may be found undergoing suppurative or gangrenous changes. 
This may be due to the fact that tumors which happen to be situated 
on exposed surfaces are invaded by bacteria, and the toxines 
of the latter excite inflammation; but there is little doubt that 



332 Tumors. 

some tumors give off into the surrounding tissues metabolic pro- 
ducts having chemotactic power and thus stimulate leucocytes 
to escape from the vessels. To all appearances we may ascribe 
to the products of disintegration occasioned by bacterial contam- 
inations and occurring in connection with the various degenera- 
tions in tumors the fact that in a number of these growths 
there occur general nutritive disturbances (oligsemia, loss of 
appetite, marked loss of strength, emaciation), which look like 
the result of a chronic intoxication — a condition known as tumor 
cachexia. 

Just as the specifically differentiated cells of the body give 
off specific products, in the same way the different kinds of 
tumor cells, as the offspring of this or that variety of physio- 
logical cells, produce in more or less similar manner the sub- 
stances characteristic of the latter ; it may be claimed that they 
too perform physiological functions.* This function, however, 
is only in the rarest instances of any service to the general 
system ; being without any relation to the co-ordinated activities 
of the rest of the organs, it is merely a vital phenomenon of 
the independent cellular complex of the tumor. The formation 
of intercellular substances by the tumor cells, as the formation 
of osteoid callus in tumors arising from periosteum, is an 
example of such function ; but tumors originating from gland- 
ular cells and having gland-like structure show this power 
especially, and are able to produce the same secretory sub- 
stances as the corresponding glands. Thus cancers of the intes- 
tinal mucous membrane secrete mucus from goblet cells; thyroid 
cancers produce colloid ; tumors of the mammary gland form a 
secretion analogous to milk (but pathologically altered), and 
tumors arising from liver cells often secrete so much bile that 
the growth becomes thoroughly infiltrated with it (icteric). E. 
Albrecht has observed that the formation of red blood corpuscles 
normally performed by the bone marrow may also be carried 
on by a tumor of the dura mater made up of endothelial cells 
and erythroblasts. 

As all offsprings of given cells manifest an ability given them 
by heredity to perform 1 the same functions as their predecessors, 
it may be expected that the metastatic nodules also show the 
same phenomenon. For example, one of a number of metastatic 
nodes which had formed in the lung from a tumor originating in 

*E. Albrecht, SitzungsbericTvt «7. morph. pliys. Gesellschaft in Miinchen, 
1901. Heft II. 



Causes of Tumors. 333 

the liver produced bile in this position. Generally the secretions 
of tumors are apt to be the seat of pathological changes, as ordi- 
narily there are no channels for discharge in the growth and the 
secretion therefore is stagnant; and moreover the function would 
be more or less abnormal, because of the abnormal topographical 
relations of the proliferated glandular epithelium, the failure of 
complete differentiation of the cells, or the reversion of tumor 
cells to embryonic type and the lack of relation with the nervous 
system of the host of the tumor. 

There are conditions however under which the secretory pro- 
ducts of a tumor are not devoid of value to the body, particu- 
larly tumors of glands which produce internal secretions of im- 
portance to metabolism and whose destruction would be ominous 
to the well-being of the body, as the thyroid gland and pancreas. 
The fact that growths from these glands may also produce 
internal secretions may in some measure compensate for the 
death or destruction of the organ by the tumor. 

[Of all the body functions, that of growth (and that is rather 
a mere vital phenomenon and not a differentiated function) is the 
one which is best and most completely manifested, being in line 
with the embryonic characteristics which tumors as a class 
possess. The example of the performance of a function of value 
to the economy selected by the author in the preceding para- 
graph is practically the only one which may be named. The 
fat which accumulates in a lipoma is of no service to the host 
of the tumor even if he be starving; the connective tissue of a 
fibroma is of no connective or supportive value, but rather a 
continual source of annoyance from' weight and pressure. Even 
the function of growth, most nearly typifying natural energy, is, 
as the author points out, irregular in the manner of its occurrence, 
is without efficient organogenic power and especially abnormal in 
that it has no definite period of cessation.] 

Aetiology of Tumors. — We possess but few facts and have but 
a meagre idea about the mode of origin of tumors. Many the- 
ories have been framed to explain the luxuriant growth of the 
cells, but the difficulty of positive proof leaves us in uncer- 
tainty between probabilities and theoretical dicta. Mere supposi- 
tions that as the result of the action of a given stimulus this kind 
or that kind of cells are excited into irrepressible multiplication. 
revert to their embryonic characteristics or undergo biological 
changes as expressed by the terms metaplasia or anaplasia, 
are in no sense satisfying, but merely serve to conceal our igno- 



334 Tumors. 

ranee of the origin of these growths and to bring into the prob- 
lem new difficulties. 

Among the more prominently urged hypotheses may be men- 
tioned the idea that an infectious cause underlies the cellular 
proliferation, a view which has had numerous adherents in re- 
cent years. At first bacteria were sought as causative factors, 
some of which as the causes of productive inflammation had mani- 
fested functions suggesting analogies with tumor formation ; 
but nothing has been shown beyond the mere secondary presence in 
tumors of various saprophytes, pyogenic and other bacteria ; and 
no microphytes have been encountered which can be regarded 
as responsible for the proliferation of cells into tumors. In time 
the line of investigation was directed to the protozoa. The in- 
clusions, often shown by a variety of methods of staining in many 
tumor cells, and apparently of foreign character (that is, intracellu- 
lar and nuclear structures not conforming to normal parts of cells), 
led a number of microscopists to regard them as of some type 
of protozoan character and as the parasitic causes of cancer and 
malignant tumors generally. However subsequent investigations 
directed to the final proof of this discovery have shown that these 
supposedly foreign elements are nothing more than altered blood 
corpuscles, lymphocytes, nuclei of the tumor cells, degeneration 
products or artefacts, produced by stains and reagents in the 
tissues. In the same way the discovery of yeast fungi having 
pathogenic properties capable of causing inflammatory granu- 
lomatous formations by inoculations in small experiment ani- 
mals, resulted in no definite or generally applicable conclusions ; 
because these blastomycetes were not to be found in true tumors, 
or if occasionally found occurred only on the surface of the 
growth and failed to give rise to characteristic tumors. With 
the demonstration of parasites as causative agents left in this unsat- 
isfactory condition, consideration should be given to the so-called 
invisible microorganisms ; or we should remember that perhaps 
with our present technique the infectious agents in question 
cannot be rendered visible. 

A number of investigators insist upon the possibility that an 
infectious factor underlies some types of tumors (Sticker), 
because as a matter of fact there have been noted a number of 
peculiar circumstances which point to the existence of a general 
extraneous (not individual) cause ; as the endemic occurrence of 
cancer, its occurrence in connection with dermal excoriations, or 



Causes of Tumors. 335 

the occurrence of dermal proliferations (papillomata) in a number 
of horses in the same stable. 

However, a great number of objections have been raised against 
the parasitic hypothesis, especially by Ribbert, which leave this 
method of causation in extreme doubt. In the first place the 
various forms of tumors always have their fixed tissue-charac- 
teristics, and the cells of the metastatic nodules invariably con- 
form with those of the original growth ; if an infection were the 
cause of the tumors it would always have to cause the production 
of the same kind of cells in the various organs (that is, the cause 
of a cylindrical cell cancer in the intestine would have to be 
able to form cylindrical intestinal epithelium in the interior of 
the liver ; the cause of a squamous epithelioma would have to 
form keratous flat epithelial cells in the lymph glands). How 
that could occur cannot be understood; it would have to be 
assumed that the cells were so intimately associated with the 
parasites that both should always go together and grow together. 
If such symbiosis be claimed to actually exist, then, as Ribbert 
logically argues, it must be assumed that the microorganism 
invariably divides at the same time as the tumor cells so that 
one of its offspring may be present in each of the two new 
cells. "If this be not essential, it may be asked how the cells 
which do not contain parasites come to proliferate any further. 
If they are able to multiply, however, without fhe existence 
of their parasites, why was it of essential importance that 
the latter should have ever been present?" (Ribbert). Then 
there is the established fact that every tumor grows from its own 
substance under direct pressure contact from the contiguous 
parts, and the surrounding tissue does not become infected ; there- 
fore the parasite would have to confine its multiplication strictly 
within the tumor cells. This would be strange ; and the question 
naturally arises, why, for example, the neighboring epithelia 
which are quite like those of a skin cancer do not furnish equally 
favorable soil for the development of the microorganisms. In 
the end, as Ribbert emphasizes, we should have to assume 
that for every new growth, for every type of cell of malignant 
tumors, there exists a special type of infectious agent incapable 
of infecting other cells, as one special form for cylindrical cell 
cancers, another for squamous cell cancers, etc. The genesis of 
tumors would become progressively more and more complicated 
if such ideas were to prevail, 



336 Tumors. 

The explanatory theories of Cohnheim and Ribbert based 
upon considerations of embryology and mechanical conditions for 
growth ate far more simple. Tumors have been repeatedly met 
in the new born ; for example a melano-sarcoma in a calf, a 
papilloma in a foal, and a number of growths, which although 
first noted in young animals were of a composition necessitating 
an embryonal origin for their development, as dermoid cysts, 
dental teratomata, branchial cleft teratomata. In the earliest 
stages of embryonic development when in a great variety of ways 
there occur formation of folds and of buds, pressure displace- 
ments and separations of the cells growing with unequal rapidity, 
it is possible that cells and groups of cells may be cut off from 
the rest, misplaced or isolated. Such misplaced cells will for 
the most part perish, because of the necessarily occurring nutri- 
tive disturbances ; but where according to circumstances the 
nutrition remains sufficient the misplaced cells will continue to 
grow and multiply, and there is necessarily produced from them 
a structure which is apparently a foreign growth and not nor- 
mally belonging to the structure of the tissues and organs. The 
formation of blood vessels probably proceeds in a more or less 
atypical manner in such separated and misplaced groups of cells, 
as a result of which their growth is in one instance a very slow 
one, in another an exuberant cellular proliferation. The experi- 
mental studies of Roux have shown that by artificial isol-ation 
and misplacement of segmentation cells each one is capable of 
growing into an embryo; and Barfurth has observed that after 
needling an egg in the gastrula stage tumor-like formations 
(denroid-like) develop from the misplaced cells. Moreover Rib- 
bert has succeeded, by transplantation of fragments of the auricle 
of .a rabbit, in obtaining polypoid nodules persisting for more 
than a year, consisting of skin, fibrous tissue, cartilage and 
bone ; and in other experiments tumor-like structures from bits 
of the notochord, by transplantation to the anterior surface of the 
intervertebral tissues. Occasionally the accidental or intentional 
operative transplantation of epithelium or bits of skin into a 
wound has resulted in the formation of a small epithelial cyst or 
dermoid cyst from the engrafted tissue, which may be regarded 
as evidence in the same line with the larger congenital growths 
of this type. The fact that experiments of this sort have thus far 
failed to produce larger tumors of progressive and persistent 
character of growth is not an argument against this theory; we 
must remember, as Ribbert insists, that our technique in artificial 



Causes of Tumors. 337 

isolation and transplantation of tissues is as yet not delicate 
enough to prevent damaging- the tissues and thus causing the 
failure of the desired results. 

Cohnheim extended his theory of the embryonic origin of 
tumors to a wider application by advancing the hypothesis that 
at an early period of embryonal development more cells may be 
formed than are needed in the construction of the organs and 
that some of these cells may remain unused as "rests," retaining, 
because of their embryonal nature, a marked capacity for prolif- 
eration ; and that from such excesses of cellular material tumors 
may develop. The views advanced by Cohnheim, to Whom we 
are indebted for first pointing out the important significance of 
fcetal isolation of cells in connection with tumor formation, are 
coming to be recognized as valid ; that from isolated segmenta- 
tion cells, which have actually been observed, tissues and organs 
may originate, and in all probability, too, independent tissue 
formations and therefore autoblastomata. 

In a somewhat different form practically the same hypothesis has been 
recently advanced by J. Beard. Beard suggests that from every fertilized 
ovum a number of germ cells originate (?), from which, however, only 
one goes to form the embryo, the remaining wandering into the embryonic 
mass and entering into the formation of the chorion (or the sexual cells?). 
It may be possible that a tumor might develop from such wandering germ 
cell if it stray to an improper part, and that such a tumor may be abso- 
lutely nothing but an incompletely developed (rudimentary) embryo (which, 
of course, is applicable for a number of tumors, especially the true 
teratomata). 

As a further application of Cohnheim's theory, which it is 
true affords a satisfactory explanation, not for all but for a 
number of tumors, Ribbert has suggested that cells may escape 
from their normal connection also in extra-uterine life and thus 
become misplaced and in consequence provide the nucleus for a tu- 
mor formation. It has been repeatedly noticed that tumors have 
developed after a traumatic lesion, at the site of injury by foreign 
bodies, after contusion, etc., as osteomata of the jaw after contu- 
sion, large chondromata in animals and man after fracture of the 
ribs at the seat of the fracture, cancer of the cheek in man after 
being hit by a stone, cancer of the lip at the place where the 
mouthpiece of a tobacco pipe has been frequently rubbing. As 
it is very difficult to think of such cases being due to any specific 
irritative influence of the foreign body which caused the injury, 
we are forced to consider changes in the positions oi the cells. 



338 Tumors. 

displacements and isolations of osteoblasts, cartilage tissue or 
epithelium, as causative of the autoblastomatous new formations. 
It is not rare to see connective tissue proliferations of considerable 
extent, completely reproducing the characteristics of fibromata, 
developing from injuries of the tendon sheaths (horse and cow) 
or of the tongue (cow) ; the growth is apparently the product of 
a chronic inflammatory process and the result of an excessive 
growth of granulation tissue. Whether some special irritant, 
perhaps bacteria, bring about such tumor-like formations, 
whether absence of tissue tension occasioned by the trauma is 
the single or principal reason for its occurrence, remains an 
open question. At all events it is recognized that there are no 
sharp lines of difference between tumors and regenerative prolif- 
erations, and that the hypertrophies, which are regarded as sim- 
ple proliferations in vacuo (as of liver) may pass over into 
tumors. 

Objections have been urged from various sides (Hansemann, 
Hanau, Ziegler) to the opinions of Ribbert (w r ho also accepts 
inflammatory processes as possible causes for the inception of cel- 
lular proliferations, as in case of epithelial cells). It has been 
urged that if the above-mentioned displacements and isolations 
of cells of epithelium w r ere sufficient to call a cancer into exis- 
tence, there necessarily should develop numberless cancers as 
results of chronic inflammatory phlegmons ; that the cells of the 
tumors ought not to appear merely as normal elements in luxuri- 
ant multiplication, but the general rule should be that there exist 
a special change, a differentiation of the cells (even though the 
causes of cellular differentiation be entirely unknown). 

Although we still await the solution of questions regarding 
the conditions which underlie the origin of tumors, and concerning 
the transformation of this or that kind of cell into tumor cells, 
it is at least certain that tumor cells are tissue elements zvhich 
have become independent and may be looked upon as cells which 
have actually become parasitic. This conception of the nature of 
tumors (for which from this point of view the name autoblasto- 
mata, proposed by Klebs, is most appropriate) has received im- 
portant support in the extremely interesting experimental studies 
of a veterinarian, C. O. Jensen. This investigator succeeded in 
carrying a carcinomatous tumor of a mouse through nineteen 
generations in mice by transplantation, and in demonstrating that 
infection played no part in the process but that the transplanted 
tumor cells, themselves parasitic upon the individuals in whom 



Causes of Tumors. 339 

they were transplanted, continued to grow and form tumors of 
the size of walnuts, growths of considerable size when that of 
the experimental animal is taken into consideration.* Earlier 
than this Hanau had succeeded in transferring an unquestionable 
skin cancer of one rat to other rats with similar results (in peri- 
toneal cavity) ; and L. Loeb and Velich have successfully trans- 
planted rat sarcomas, and Moran has transplanted adenocarcin- 
omata of a white mouse a number of times. [Still more recently 
L. Loeb has carried an adenocarcinomatous tumor of a Japanese 
dancing mouse through a number of generations, eventually find- 
ing a change in the nature of the tumor which took on the histo- 
logical characteristics of a spindle cell sarcoma. Other investi- 
gators have described similar success in transplantation ; and 
Loeb's instance of change in the tumor characteristics is not an 
isolated one.] (Attempts to transplant sarcomas and can- 
cers in dogs undertaken as much as ten years ago by Ptitz and 
other investigators have thus far failed.) The point of special 
interest in Jensen's studies is the discovery that it is possible, 
by special methods of implanting the tumor cells, to render the 
diseased mice immune so that the tumors, which are present in 
them and which are ordinarily fatal, disappear and the subjects 
recover. Jensen brought about this result in two ways, first by 
treating the diseased mouse with its own tumor cells, substances 
developing in consequence in the blood (cytotoxins), which in- 
hibited further extension of the tumor cells at the original site 
(v. Chapter on Immunity) ; and second by repeated introduction 
of the tumor cells into rabbits (not susceptible to the mouse 
carcinoma) he obtained a serum which manifested specific cyto- 
toxic action. [In a similar set of transplanted adenocarcinomata 
of mice Gaylord found that some of the affected individuals re- 
covered naturally, their tumors after more or less growth under- 
going atrophy and disappearing. From such individuals he ob- 
tained a serum which, when introduced into mice with marked 
tumor growths, uniformly caused their disappearance by its 
cytolytic power.] 

The tissue of tumors isolated from the body will retain its vitality at 
a temperature of from i°-3° C. for about eighteen days, at room tempera- 
ture for about twelve days, but at body temperature for scarcely twenty- 
four hours. This difference is supposed to be due to the colls passing 
into a sort of resting condition at the lower temperatures, while at the 
body temperature they cannot avoid metabolism. 

♦For details v. Cc>itr<ilbl. f. H<il;ttriol. u. I><ir<txitcnlnt>i<lc, L908, No. 1. XW1V 



340 Tumors. 

Statistics of Tumors in Animals; Influence of Age and Sex.— It has only 
been within very recent times that any attempt has been undertaken to 
systematical!}' collect the material relating to the frequence of tumor occur- 
rence in animals (Johne, Frohner, Casper, Sticker). It is very difficult 
at the present time to draw an}- comparison of these data with those 
of man whose tumor involvements have for many years been subjects 
of careful, conscientious and extensive statistics in literature. The early 
slaughtering of the food animals is partly at fault, as many tumors are 
not apt to appear until advancing age. This is especially true of cancer, 
according to Frohner ; which in dogs is not encountered at all for the first 
two years, and is met with any degree of frequency only in old dogs ; 
eighty-seven per cent, of his animals affected with cancers were over five 
years of age, fifty-four per cent, over seven years old (in man cancer is 
most frequent between the fortieth and seventieth year — about seventy per 
cent.). While in man cancer is of special frequence on the lips, stomach 
and uterus, in these sites the tumors are very rare in animals (gastric 
cancer has been observed but one time in the dog — Eberlein). Sarcomata, 
however, are mainly met in young animals. 

As far as sex may have influence upon tumor formation, it can merely 
be said that the female sexual apparatus in animals is far less frequently 
involved by malignant tumors than in mankind ; only in the mammary 
glands of bitches are various tumors to be met with any frequence, while 
cancers of the genital tract occur only as great rarities. 

As indicative of an influence exerted by the species upon the devel- 
opment of tumors, it may be stated that cancer is relatively frequent in 
dogs, melanosarcoma and cancer in horses, and sarcomas in cattle and 
swine (Casper). 

Resume of Tumors. — The nomenclature and classification of 
tumors is, as explained on p. 326. mainly dependent upon their his- 
togenesis, origin and tissue composition. The existence of many 
types of component tissues, together with the fact that cells of mul- 
tiplying tissue may present all sorts of shapes, and that sometimes 
unusual tissues take part in the formation and that it is often im- 
possible to determine from what normal type of tissue the tumor 
had its origin, make it difficult to carry out the classification 
strictly upon this basis. A certain number of tumors present 
themselves always in the same forms and these can be sharply 
defined ; but there are others which are of mixed structure and 
of intermediate types. 

The principal types of tumors may be distinguished as fol- 
lows: 

1 — Fibroma, simple fibrous connective tissue tumor or fibrous 
tumor. 

2 — Lipoma, fatty tumor. 
3 — Myxoma, mucoid tumor. 



Fibroma. 341 

4 — Chondroma, cartilaginous tumor. 
5 — Osteoma, bone tumor. 
6 — Myoma, muscular tumor. 
7 — Neuroma and Glioma, nerve tumors. 
8 — Hemangioma, Lymphangioma, vascular tumors. 
9 — Sarcoma, atypical connective tissue tumor. 
10 — Lymphoma, lymph gland tumor. 
11 — Melanoma, pigmented tumor. 
12 — Endothelioma, Perithelioma, Cholesteatoma. 
13 — Papilloma. 

14 — Adenoma, epithelial glandular tumor. 
15 — Carcinoma, atypical epithelial cancer growth. 
16 — Epithelial cysts, Dermoids (skin tumors), Odontoma, Com- 
pound Teratomata. 

The Individual Types of Tumors. 

Fibromata. 

A fibroma, or fibrous connective tissue tumor; is a growth 
made up of adult fibrous connective tissue, that is, of connective 
tissue cells, fibrils and bloodvessels. 

Fibromata vary in consistence with the degree of predom- 
inance of their fibrillar basic substance, with the density or 
looseness of the bundles in which the fibres are united and the 
relative presence, of blood vessels and lymph vessels. From this 
point of view two types of these tumors are distinguished, the 
hard and the soft fibroma. 

The hard fibroma (fibroma durum) is met as rounded nodes 
of very dense consistence, usually presenting the firmness and 
appearance of tendon tissue, cutting with a tough resistance and 
creaking on section. The cut surface which shows but little 
moisture and is nearly dry, is of a white or light yellow color, 
with intermingled shining and dead white markings from the 
intricately interwoven bundles of fibres (depending on whether 
these are cut in longitudinal or transverse planes of section), and 
with a fibrous appearance. The tumor as it expands in growth 
is usually sharply defined, presses upon the adjacent structures 
and has no tendency to penetrate them ; the surrounding tissue, 
however, being thinned more and more as the layer oxcv the 
growth is stretched. The stretching and loss of tissue tension 
may cause coincident proliferation of these adjacenl structures, as 
epithelium, over the tumor. Under the microscope the bundles 



342 Tumors. 

of fibres, compactly arranged and thick, may be seen running in 
a wavy course, usually arranged concentrically about the blood- 
vessels and often of considerable length. Between the fibres are 
spindle cells with spindle shaped nuclei, and occasionally elastic 
fibres are intermingled. 

Sometimes the fibroma develops as a diffuse growth, giving 
rise to large wooden-like thickenings of the subcutaneous tissue, 
with radiating extensions running into the surrounding struc- 
tures. 



9 . 




S 

S* 



Fig. 86. 
Hard fibroma : subcutaneous nodule, from horse. 

The soft fibroma (fibroma molle) is characterized by its softer 
consistence, and the greater proportion of bloodvessels and lym- 
phatics in its construction. It is in consequence of a more reddish- 
gray color, is sometimes gelatinous ; and its shape is sometimes 
nodular or lobulated, sometimes with a villous papillary surface. 
Under the microscope it contains in addition to the loosely ar- 
ranged bundles of fibres numerous spindle and rounded connec- 
tive tissue cells and wandering corpuscles, and is quite rich in 



Fibroma. 



343 



blood vessels. The soft character of the growth is due partly to 
the numerous cells it contains, partly to the presence of lymph 
fluid, especially where the latter is practically stagnant because 
of twisting of the pedicle of a pedunculated tumor. In such cases 
the bundles of fibres and cellular groups are separated from 




Fig. 87. 
Fibroma (myxomatous) Of llu> end of cow's tail. 



344 



Tumors. 



each other and meshes are formed and become more or less dis- 
tended, and the cells take on branched, stellate shapes. Such 
a growth is also known as fibroma myxomatodes or fbromyxoma 
from the gelatinous change present in it ; the more vascular 
reddish ones as raspberry polyps, fibroma an gio mat odes, caver- 
nosum or teleangiectaticum. 

Occasionally calcification or even ossification takes place in 




Fig. 88. 
Section of a fibroma from a horse. 



the tissue of fibromata, producing dull white foci of bony hard- 
ness {fibroma petrificans, ossificans). 

Sometimes the fibrous tissue formation is found about the 
bloodvessels or about the glandular ducts or nerves, arranged in 
circular concentric whorls and systems of bundles about these 
structures ; such growths being described under the terms plexi- 
form or pericanalicular fibromata. 

Fibromata growing from scars or imperfectly cicatrized granulation 
tissue from wounds are apt to become especially dense, consisting of thick, 
closely packed, interwoven bundles of fine fibrils, are known in human 



Fibroma. 345 

medicine as keloids (x&y, the claws of a crab), because of the resemblance 
of the rounded or finger-like nodes to the legs of a crab ; in man spon- 
taneous keloids are encountered as tumor formations, apparently hereditary 
in families. 

The fibromatous tissue may combine with fat tissue, bone or 
muscle giving rise to fibrolipomata, Hbro-osteomata or fibromy- 
omata, or, when the second type of tissue predominates, to lipo- 
Hbromata, osteo fibromata or myoHbromata. [It is not a matter 
of special importance, but generally the name of the tissue 
predominating is given as the basic name of the combined tumor, 
contrary to the above statement. Thus where in a tumor com- 
posed of fibres and adipose tissue the former predominates the 
growth is known usually as a lipofibroma : where the latter is 
the more important constituent, the term fibrolipoma is used.] 
In case of an associated proliferation of the epithelium 
covering a fibroma, or of glandular tissue the resultant com- 
binations are known as Hbropapillomata and fibroadenomata. 
Soft fibromata, more particularly because of active proliferation 
of their cells and from the fact that these young cells are not apt 
to maintain uniformity of shape but assume in varying measure 
embryonal characteristics in size and shape, occasionally acquire 
features which may justify the name fibrosarcoma. 

Fibromata are of slow growth, usually single tumors, but 
sometimes primarily multiple, ranging in size from that of a 
nut to that of a human head or even larger, being known to 
weigh as much as one hundred, and even one hundred and sev- 
enty-eight kilograms (Wehenkel, Siedamgrotzky). Because of 
the wide distribution of fibrous connective tissue structures 
their development may take place in practically any part of the 
body, although there are certain parts in which they appear with 
especial frequence. The places of election are the skin and 
subcutaneous tissue, especially of the front of the breast (horse), 
the dewlap (cow), the elbows (dog), and the end of the tail 
(cow). In these situations they form hard nodular swellings 
or nodes covered with epidermis, or in other instances lobulated 
pedunculated growths (fibroma pendulous). As multiple pri- 
mary formations Siedamgrotzky once counted in a thirteen-year- 
old stallion more than a hundred fibromata in the skin, which had 
grown in the course of three months in the breast, abdomen, 
neck and face, to sizes varying from that of a hazel nut to that of 
the palm of the hand. Similar multiplicity, warranting the term 
fibromatosis, has been observed in dogs by Frohner and Cadiot 



346 Tumors. 

(cited by Casper). Fibromata are frequently found in the tongue 
of the cow, as well as in the vagina, in the latter situation as 
pedunculated growths of large size projecting into the vaginal 
canal. Those fibromata which are found in horses and cattle 
after injury of the skin and tendon sheaths at the joints of the 
feet may form enormous masses ; they are apt to have the sur- 
faces covered with granulation tissue. Fibromyxomata are es- 
pecially common at the end of the tail and in the heart (epicar- 
dium and endocardium) as pedunculated growths, as well as in 
the naso-pharnyx (where they are found hanging from the wall 
covered with mucous membrane and are known as nasal polyps). 
The author has observed a perfect string of hard rounded fibro- 
mata in the lung of a horse (for details v. Kitt, Lehrbuch d. 
speziellen pathol. Anatomie d.^Haustierc, Verb v. Enke, Stutt- 
gart, II. Aufl., 1901). 

A fibroma may sometimes be harmful because of its size and 
location (occlusion of passages, pressure upon vital organs), but 
does not give rise to metastasis and usually does not recur after 
extirpation. 

The hard fibromata of the skin and tongue undoubtedly are 
often results of traumatic lesions. The connective tissue scle- 
roses resulting from injuries by foreign bodies, or that arising 
after healing of an actinomycotic area, a chronic botryomycosis 
or even a malignant cedemato'us infection, may be sometimes 
such hard, definitely outlined, biscuit-shaped or nodular deposits 
and prominences that an anatomical distinction between these 
sequels of chronic productive inflammation and true tumors can- 
not be made. 

Lipomata. 

The lipoma or fatty tumor is made up of adipose tissue, of 
clusters of fat cells in various stages of development, along 
with bloodvessels and fibrous connective tissue. The fat cells 
are apt to be larger than those of normal adipose tissue. These 
tumors arise from situations normally rich in adipose tissue, .as 
the mesentery or subserous peritoneal fat, where they frequently 
occur in the horse. The peritoneal adipose tissue often forms 
lobular appendages, which when much overgrown and stretched 
by the intestinal movements become pedunculated and present 
themselves as pearshaped masses or tumors of the size of a fist. 
They may give rise to fatal intestinal entanglements. In case 



Lipoma. 



347 















Fig. 89. 
Lipoma. 




Fig. !><>. 
Loop of Intestine of horse strangulated from the entanglement of a lipoma. 



34-8 Tumors. 

of rupture of the pedicle such lipomata become loose in the 
peritoneal cavity and may be found at autopsy as compressed 
free bodies. These peritoneal lipomata present a smooth surface, 
are semitransparent, yellowish or white. Lobulated lipomata are 
found also in the cow and hog in the omentum, and in the intes- 
tine and perirenal fat; in these animals the fat is firm and white. 
The subcutaneous tissue is a frequent site in the horse, especially 
in the neighborhood of the knees where they may attain very large 
size (twenty-six and a half kilograms in a case reported by 
Moller) ; and in the dog especially on the inner surface of the thigh, 
in the fold of the knee (Frohner), and in the breast (Stockfleth). 
As submucous growths they have been found in the uterus (a lipo- 
ma of a cow recorded by Lund reaching a weight of seventy-five 
kilograms), and in the membrana nictitans in the horse and dog 
(Frohner). Here, too, their shape is nodular or lobular and the 
growth is usually well circumscribed and therefore easily shelled 
out. 

Sometimes lipomata appear in positions where adipose tissue 
does not normally exist; thus two lipomata of the size of a 
child's head have been found in a dog's liver by Trasbot, small 
lipomata in the kidneys of the same animal (Bruckmiiller), and 
Kiihnau encountered a rare instance of a lipoma of the brain in a 
three-year-old beef (four centimeters in diameter, rounded and 
arising from one of the bloodvessels of the pia mater). This 
last instance was congenital. According to Bostrom it is pos- 
sible that a bit of germinal fat tissue of the skin of the embryo 
might have been separated and been misplaced in the cranial 
area. Lubarsch suggests that intraparenchymatous renal lipo- 
mata take their origin from portions of the renal capsule. 

Lipomata occur as either single or multiple primary growths. 
They may occasionally undergo mucoid degeneration (lipoma 
myxomatodes) , calcification (lipoma petriiicans) or dry anaemic 
necrosis. When the combined fibrous connective tissue is espe- 
cially abundant they may be very firm (lipofibroma). They 
are slow in growth, but as above stated may attain considerable 
size. Those which are situated subcutaneously may be easily 
extirpated ; they are not recurrent and do not give rise to 
metastases. 



Tumors. 349 

Myxomata. 

. A myxoma, a mucous connective tissue tumor, is a neoplasm 
which consists either entirely or in part of gelatinous embryonic 
connective tissue; and therefore its tissue closely simulates the 
Wharton's jelly of the umbilical cord in consistence, transparency 
and texture. It is characterized microscopically by an intercel- 
lular substance rich in mucin, in which are sparsely scattered 
cells of spindle and highly branched stellate forms with long 




,: 4j 



s 



Fig. 91. 
Myxoma. 

slender prolongations; while here and there are to be seen blood 
vessels and a small amount of fibrillar connective tissue. In 
fresh material the mucinous substance may be precipitated by 
the addition of acetic acid. Often only individual portions of 
the tumor are conspicuously myxomatous, the remainder being 
made up of fat tissue or dense fibrous tissue (myxolipoma, jiiy.vo- 
iibroma) ; and many luxuriantly growing types show features 
of transition to sarcoma and mixed tumors (myxosarcomata). 
Occasionally fibromata and lipomata of pedunculated shape. 



35o 



Chondroma. 



which have become cedematous from lymphstasis, simulate 
myxomata (fibroma myxomatodes), the absence of mucin or its 
scanty proportion in the fluid content distinguishing them from 
the true myxoma. 

Myxomata develop as single or more or less multiple primary 
growths according to their situation, and as sarcomatous mixed 

tumors capable of metastasis and of 
embryonic appearance. They are es- 
pecially met upon and in the heart 
of cattle (when the subpericardial 
and subendocardial foetal mucous tis- 
sue acts as their developmental sub- 
stance) as rounded, lobulated growths 
ranging in size from that of a nut to 
that of a fist ; they also occur in the 
nose in the cow and horse, in the 
parotid, and in one case in the dog 
around the spinal cord (Holzmann), 
and, too, in cattle along the nerve 
trunks (neuromyxoma). The gela- 
tinous, glassy, swollen, yellowish 
(sometimes like flesh of the cod- 
fish) appearance, their softness and the ropy mucoid character of 
their substance, constitute their important distinguishing features. 




Fig. 92. 

Myxofibroma of the heart, from 
cow. 



Chondromata. 

A chondroma or cartilaginous tumor has, in addition to a 
vascular fibrous connective tissue framework, as its main con- 
stituent cartilaginous tissue, usually of the hyaline type, and 
contains cartilaginous cells of very irregular size encapsulated in 
this substance without regularity of arrangement. The fibrous 
tissue forms a capsule and the trabecular framework about the dif- 
ferent cartilaginous areas (which occur as islands and lobulated 
nodules in the tumor) and acts as their nutritive perichondrium. 

Besides the pure chondromata there are met many mixed 
types, made up of fibrous tissue, bone and glandular tissue, in 
which cartilage enters as only one of the constituents ; and modifi- 
cations may also result from the rather marked tendency of the 
cartilage to metamorphosis, both regressive and progressive. Mu- 
coid degeneration with production of gelatinous softened foci 
(cysts), and calcification, giving rise to white opaque patches 



Chondroma. 



351 



(chondroma cysticum, myxomatodes, pctriiicans) are especially 
likely to be observed; and sometimes ossification (chondroma 
ossificans) takes place. 



<? 





Fig. 93. 
Chondrofibroma of ovary of sheep (the uterus to the left). 

Chondromata are nodular, nodose, lobulated, rounded tumors 
of dense (in case of myxomatous change or when other tissues 
are combined they are softer) consistence ; showing their car- 
tilaginous substance as a milk-white, grayish and bluish white, 
semitransparent material. They may attain considerable dimen- 
sions, perhaps the size of a human head, and may weigh from 
ten to twenty-eight kilograms. According to their location the 
cartilaginous tumors may arise from previously existing cartilage 
(ec chondromata) , or may develop within the bone marrow or in 
the soft tissues which do not contain cartilage (enchondromata) . 
The former originate from the perichondrium, the cells of which 
are usually concerned in formation of cartilage; the latter arise 
probably from misplaced embryonic cartilaginous rudiments. 



352 Tumors. 

Isolations of bits of tissue from either of these sources may occur 
in embryonic life from developmental faults, as in the formation 
of the branchial arches or the primitive vertebrae and embryonal 
elements of the ribs. The fact that chondromata may be congen- 
ital is an argument for this view. In the postfcetal period car- 
tilaginous isolations may take place from disturbance in growth 
in the skeleton (rachitis) ; and traumatic lesions, as fractures of 
ribs, may give origin to separation of bits of perichondrium, and 







'i " 



" - - "-":"-."■-" ' -V' »'-V'-X. 

Ik ^^,^^w : ::,:..;,.-,,u^-/- 



>v 



■'•'■•. ■■'•."■ ■'•' •::%'•-- • "V'j>r<.-v ; ."»"-^,- .', ' «'* " . >'• •;*■.•<•'• v.. ;'.. 'VMhwa 
'-.-•■. •''■•! •*■''';'•'> '. r ■,,-.-.% » V. • • ••; •••»•/ •- .V- : > .-"•'■■■'• i 




.,-••, .• •> . .•-.•.■.-•?.r/vi' .■ i- 




■ .» . »-. *< *** 

. . ■ •-.'. ;.- ::;..-"Yvl>>' 

Fig. 94. 
Section of a chondroma from a hen. 

these in association with profuse callus formation might develop 
into chondromatous tumors. 

Chondromata are most common in the bony framework of the 
chest as the result of fractures of the ribs, projecting into the 
chest cavity or beneath the skin as large tumor masses ; they are 
also frequently met in the neighborhood of the jaw and thyroid 
gland, originating from remnants of the branchial cartilages, in 
goats, horses, dogs and cattle. As mixed growths (chondro- 
adenoma) they have been seen a number of times in the lungs, 
mammary gland and in the testicles in animals. As exceptionally 
rare instances may be mentioned enchondromata of the vitreous 



Osteoma. 353 

humor of both eyes in a congenitally blind colt (Renner), and 
a chondroma the size of a fist in the wall of a calf's stomach 
(first stomach). 

.A chondroma should be looked upon as a dangerous growth, 
at times because of the position it may occupy, but also because 
of its usually marked tendency to grow large, and further because 
it can give rise to metastasis. The cartilaginous masses hap- 
pening to penetrate by growth into the veins sometimes develop 
long processes within the lumen of the vessels, which are of 
course obstructed ; and any little portions which may be carried 
away by the blood may form metastatic nodes in other organs. 

In man there are seen from time to time pea-sized growths of cartilag- 
inous tissue, peculiar in the marked vacuolation of their cells and in their 
gelatinous consistence, at the base of the skull in the neighborhood , of the 
spheno-occipital suture; these, because of the bladder-like, swollen character 
of the cells, were formerly known as ecchondromata physaliformia, but are 
recognized to be remnants of the notochord and are called chordomata. 

Osteomata. 

By the term osteoma or bone tumor is meant a definite new 
formation presenting the structure of bone tissue and its mar- 
row. According to the density of the calcified bone substance 
there are distinguished (1) the eburnatcd osteoma (osteoma 
ebumeum) which is of ivory-like hardness like the dense cortical 
bone; (2) the spongy osteoma (osteoma spongiosum), of a more 
cancellous type, containing considerable marrow substance ; and 
(3) the medullary osteoma (osteoma mcdullosum) composed 
principally of marrow. In most instances the structure of the 
bone (calcified matrix in lamellar arrangement about Haversian 
canals, bone corpuscles in lacunae, bloodvessels, marrow cells 
and fat) is characteristic ; but. often as far as the marrow is 
concerned, abnormalities are common, the medullary spaces being 
occupied perhaps rather by spindle cells and fibrous connective 
tissue (osteofibroma) or showing special abundance of round cells 
and giant cells (osteosarcoma). Where the bone trabecula have 
no lamellated structure and the bone corpuscles do not show 
the usual projecting branches the specimen is spoken of as an 
osteoid sarcoma. 

In many cases it is difficult and even impossible to determine 
whether a tumor-like osseous growth is really ^\ autoblasto- 
matous origin or is the product of inflammatory proliferation, 
because definite lines of separation between tin- two cannot be 



354 Tumors. 

drawn. For this reason usually only the more massive, large and 
clearly denned bony growths are called osteomata, and the rest 
are known collectively as osteophytes. The small protuberances, 
of the size of a pea to that of a nut, projecting from the surface 
of bones, are also called exostoses; the flat superficial thickenings 
around bone shafts, periostoses; those which grow along bones 
as bony formations in fascise and connective tissue, parostoses; 
an ivory-like, hard, well-defined formation in the interior of 
bones, an enostosis. Diffuse thickenings of the bones in the 
skeleton from osseous hyperplasia are known as hyperostoses; 
osteophytes with cartilaginous coverings, as cartilaginous osteo- 
phytes. 

The osteophytes and osteomata growing from the skeleton 
develop principally from the osteoblastic layer of the periosteum 
or from cartilaginous developmental bases (anlage) ; some are 
congenital or from their position may be looked upon as caused 
by disturbances of embryonal development and as referable to in- 
clusive misplacement of bits of the embryonic bone tissue af- 
fected. This view is especially applicable to the rather common 
large osteomata of the head cavities (cattle, horses), arising from 
the sphenoid, ethmoid or the turbinate bones ; in their gradual 
enlargement they press upon the surrounding bony walls, force 
the jaw and nose out of position, project into the maxillary sinus, 
nasal cavities or into the orbit or cranial cavity, and obstruct 
these spaces with continuous pressure upon the respective soft 
parts. Other forms which are located on the outside of bones, 
sometimes as broad expanded growths or arising from slender 
pedicles, probably are caused by traumatic influences ; and the 
exostoses which are met commonly in the under jaw of the horse 
apparently arise from isolated osteoplastic foci ; and the large 
osteomata on the horn process in cattle are probably due to loss 
of tissue tension caused by injury to the horn capsule. 

A remarkable variety of pathological bone proliferation is the 
progressive ostcitosis met with in young dogs. It consists in 
the occurrence of bone formation at the places of attachment 
of the tendons and muscles of the lower jaw and extremities, 
causing as it progressively advances an atrophy of the muscles 
and giving the animal a stiff awkward gait ; it is accompanied 
by marked thickening of all the bones of the skeleton. The 
disease is similar to the affection in man known as myositis 
ossificans progressiva, and is apparently an abnormality of de- 
velopment, in which as Ribbert supposes the intermuscular con- 



Osteoma. 



355 



nective tissue acts as a derivative of the periosteum. In fresh 
specimens the periosteum and muscular connective tissue of 
these cases appear to be merged into one mass of bacony, cartila- 
ginous and rigid character; after maceration, brittle, papyraceous 



«^&3fe^£ 



' gjK, ' ; , 





Fig. 95. 
Osteoma on the horn process of a cow. 



and gland-like plaques and nodosities of bone are found along 
the muscular attachments. 

Osseous growths of irregular and flat shape (ossificatio 
racemosa, plana) and intermediate types approaching compact 
osteomata have been encountered as isolated deposits and in combi- 
nation with cartilage and fibrous tissue occasionally in the lungs 
(cow), peritoneum and mesentery (cow, hog, dog), upon and 
within the udder (cow, dog), testicles (horse), in the vitreous 
humor of the eye (horse), and in the right cardiac auricle of the 
horse. The attempt to explain the origin of these bone forma- 




Fig. 96. 
Section of above osteoma of horn process. 



tions must rest with the assumption of the possibility of a meta- 
plasia of fibrillar connective tissue into a calcified matrix, with 
transformation of the connective tissue corpuscles into bone cor- 
puscles. 



356 Tumors. 

Myomata. 

A myoma or muscle tissue tumor is composed of muscle 
fibres, together with an accompanying vascular connective tissue. 
Corresponding with the two varieties of muscle, these tumors 
occur in two forms, one, the leiomyoma {myoma Icevicellulare) , 
composed of smooth muscle cells, and the other, rhabdomyoma 
(myoma strio cellular e) , a tumor made up of transversely striated 
fibres. 

The latter (rhabdomyoma) is a very rare tumor; and never 
shows the muscle tissue in a state of perfect development like 
that of the muscles of the body. The muscle fibres are rather of 
an embryonic type and are usually mingled with embryonic con- 
nective tissue (rhabdomyosarcoma, rhabdomyoma sarcomatodes) 
or combined with glandular tissue in addition (rhabdomyoaden- 
osarcoma). The muscle fibres are thinner than normally, 
ribbon shaped ; their transverse striae are not complete and are only 
apparent along the edges of the fibres, a richly nucleated sarco- 
plasm occupying the interior of the fibres. Numerous spindle 
cells with longitudinal striations may be noticed in addition, 
which may be looked upon as early stages or as muscle fibres per- 
sisting in undeveloped condition. These muscle elements are not 
arranged in compact parallel bundles but are scattered about in 
irregular manner. They are therefore not of as deep red a color 
as normal striated muscle, having rather a pale reddish-gray 
tint. They occur as more or less well defined nodes ; and rarely 
occur in situations where striated muscle tissue exists normally 
but rather in complete heterotopism, in organs which have no 
such basic elements. This would indicate that rhabdomyomata 
originate in muscle germinal tissue misplaced in embryonal life. 
This is doubtless true of the tumors in question which develop 
from the kidney, the muscular elements in their structure appa- 
rently originating from misplaced portions of the myotomes of 
the primitive vertebral column. Johne has recorded an adeno- 
sarco-rhabdomyoma of this type from the kidney (hog) which 
weighed fourteen kilograms. (In man rhabdomyomata have 
been recognized frequently in the kidneys, testis, uterine wall, 
urinary bladder and the oesophagus.) Besides the case above 
mentioned, contributed by Johne, there are only two instances of 
rhabdomyomata in animals recorded in literature (Casper). One 
was observed by Gratia in an old horse in a dissecting room, a 
fusiform tumor about eight or ten centimeters in length, in the 



Myoma. 357 

vagus nerve trunk about the middle of the neck; the other was 
found by Kolessnikow, growing in the tail and perianal con- 
nective tissue of a twenty-year-old stallion, a tumor containing 
pigment cells (rhabdomyosarcoma melanodes), which had given 
rise to numerous metastases in the liver, spleen, peritoneum and 
pleura. 

The leiomyoma is found more frequently and in easily recog- 
nized forms in animals : in case of extensive combination with 



7v - • 










{ Ktf 


l^c***** 5 " ****: ■""*■* 


*s^ v 





Fig. 97. 
Leiomyoma (from uterus) : a, place showing bundle of muscle fibres cut transversely. 

fibrous connective tissue, as may sometimes be seen, the growth 
is spoken of as a myofibroma. These tumors always develop 
in a structure rich in smooth muscle, and are consequently met 
principally in the muscular wall of the uterus and vagina (in cow 
and hog, less frequently in the dog), of the intestine and stomach 
(horse), urinary bladder (dog), now and again in the testis 
(horse), and in the subcutaneous tissue (horse). They are 
rounded or globular, firm tumor masses, which arc sometimes 
found projecting from their places of origin, covered over 
smoothly with mucous or serous membrane, presenting on their 



358 Tumors. 

cut surface a fibrous or striated appearance, of a reddish-gray or 
pale gray color. Especially the leiomyomata growing from the 
uterus and hanging to this organ in the peritoneal sac, may attain 
enormous size, possibly as large as a well filled horse's stomach, 
weighing from thirteen to thirty-six, to one hundred kilograms. 

The smooth muscle fibres, easily recognized by their long 
fusiform shape and rod-shaped nuclei, are arranged parallel to 
one another in bundles interlacing in every direction with each 
other in confused manner. In sections the fascicles are found 
cut longitudinally, obliquely and transversely, and between these 
the vascular connective tissue may be observed in variable 
amount as clearer threads. In pedunculated examples where the 
myomata have in consequence been subject to twisting, circu- 
latory disturbances are often determined, as results of which 
congestive haemorrhages, cedematous appearance, anaemic necroses 
and fatty degeneration may take place in the tumor mass. 

In man epithelial inclusions and hollow tubules have been 
noted in the myomata of the genital organs, this histological 
feature giving support' to the view that the myoma in this 
situation is related to embryonal disturbances which have occa- 
sioned misplacement and isolation of portions of the Wolffian 
body or of the Miillerian ducts (adenomyomata) . 

Leiomyomata are usually single primary growths [in human 
beings they are often multiple] , and give rise to harm only 
by their volume. They are not recurrent tumors [and are no't 

metastatic] 

♦ 
Neuromata and Gliomata. 

A neuroma, or nervous tissue tumor, strictly speaking must 
be made up of nerve fibres or gangliomic cells in luxuriant prolif- 
eration, accompanied by a supporting framework and by bloodves- 
sels. If we exclude the terminal thickenings of nerve stumps 
occasionally occurring after neurotomy, the so-called amputation 
neuromata (v., p. 250), from the list of true tumors (because their 
growth ceases after a time), it may be said that the formation of 
true neuromata in animals has as yet never been certainly proved 
to occur. Even in man but few instances of this type of neoplasm 
are known, situated in the sympathetic area (especially cceliac gan- 
glion and pelvic plexus), as no4es ranging up to the size of a 
child's head. 

The growths summarily designated by the name neuroma in 



Neuroma. 



359 



the literature are neurofibromata and neuromyxomata, tumors 
which develop in corded, fusiform or cylindrical thickenings up 
to the size of a finger, or in nodular shape up to the size of a 




Fig. OS. 
Neurofibromatosis of brachial plexus of cow. 

potato, on the nerve trunks. Their formation results from a 
marked proliferation of the perineural connective tissue and 
nerve sheath about the nerve fibres. The proliferated mass has 



360 Tumors. 

a grayish-red, semitransparent appearance and usually extends 
along many adjacent nerves as a nerve plexus, giving rise to 
an extensively intertwining growth (plexiform or vine-like neuro- 
fibroma). Tumors of this kind have been observed, especially in 
cattle, involving the brachial plexus and the dorsal, costal and 
sternal nerves (Ostertag, Morot, Blanc, author's personal obser- 
vation), and producing in these structures hundreds of nodular 
thickenings. Morot counted in one case thirteen hundred and 
fifteen neuromyxomata in an old cow and traced them even to 
the nerves of the pharynx and heart. Leisering observed similar 
growths in a horse with extensive involvement of a number of 
nerve trunks. 

An embryonic developmental disturbance of unknown nature 
has been regarded as the basic factor for the neurofibromata and 
neuromata observed in man. because the growths have been met 
as congenital and inherited faults. 

Glioma or ncuroglionia. the tumor of nervous connective tis- 
sue substance, is produced by proliferation of the glia cells of the 
central nervous system or the granular layer of the retina of the 
eye, and occurs primarily only in these two positions. In animals 
it has been recognized with certainty but twice, once by Gratia 
in a dog's brain (ganglion Gasseri) and again by Piana in the 
spinal cord of a dog, in both instances causing palsies from 
pressure upon the central nervous substance and the emerging 
trunks. 

The gliomata of the human brain are usually embedded in 
the brain tissue without sharp definition from the latter and are 
so merged with it that they are only recognizable as diffuse 
grayish or reddish firm areas. They are made up of protoplasmic 
cells with numerous fibrils projecting in a radiating fashion from 
all sides of the cell (spider cells, astrocytes) ; and in this fibrillar 
meslrwork there are in some instances also present polymor- 
phous sarcomatous or ganglionic cells, and epithelial inclusions 
may be observed (spaces lined with cylindrical epithelium). This 
last feature and the occurrence of these growths in newly born 
children confirm the belief that disturbances of development of 
the cerebral vesicles are the basis of these neuroglia growths, for 
example isolation of offshoots from parts covered by ependyma 
(perhaps, too, transformation of the glia cells to embryonic cel- 
lular type, the glia tissue being originally an epithelial tissue 
differentiated into a supporting material). 



Glioma. 361 

Retinal gliomata of man spread out as grayish nodular tumors 
over the inner surface of the globe of the eye, but are also met per- 
forating the sclera, growing along the optic nerve and perhaps es- 
caping into the orbit ; they occur as congenital growths sometimes 
involving both eyes, and have been observed in a few instances in 
several children of the same parents. For these reasons and be- 
cause of their structure they may invariably be referred for their 
origin to developmental faults. They are only in part composed 
of glia tissue, being principally made up of neural epithelium of 
the retina reverted to embryonal type, arranged in thick sheath- 
like layers around the synchronously proliferating bloodvessels. 
[These so-called retinal gliomata are the subject of considerable 
controversy. The presence of any true glia tissue comparable 
to that of the brain is in itself questionable, and the evident part 
taken by the retinal neuroepithelial tissues has led to their being 
denominated neuroepitheliomata. These neuroepithelial cells are 
frequently found in a so-called rosette arrangement, as the cylin- 
drical epithelium seen in sections of small ducts. The tumor in 
its infiltrating and metastatic character is a very different growth 
from the glioma of the brain ; the former is rapidly fatal, while 
the latter shows little tendency beyond a slow peripheral infiltra- 
tive enlargement to extend, and persons may have harbored these 
growths for years with little definite evidence of their presence. 
The more separate arrangement of the cells of the true glioma, 
the branching fibrils of the cells preventing close adjustment, is 
not seen in the retinal glioma, whose cells are very closely packed and 
evidently have but few and insignificant projections upon them 
(in fact one must examine with great care even after special 
staining to think that these projections exist in any comparable 
degree). The editor would regard favorably the separation of 
these growths from the class of true gliomata, preferring the 
more distinctive and well justified term of neuroepithelioma. 

The true glioma of the brain is usually single ;. sometimes sev- 
eral have been found, usually in close relation and probably in 
reality representing the same growth. When pure and free from 
sarcomatous combination the tumor should be regarded as rela- 
tively benign save for its pressure effects. Distant metastasis is 
rare; although local metastasis from peripheral infiltration is 
the rule.] 



362 



Tumors. 



Haemangiomata and Lymphangiomata. 



The hemangioma, or blood vessel tumor, is made up of dis- 
tended and proliferated vascular tubes filled with blood, together 
with the connective tissue supporting these vessels. Strictly speak- 
ing, a true vessel tumor must consist for the most part at least of 
vessels which have been newly formed, and should not be a tumor- 
like enlargement made up simply of pre-existing vessels which 
have become enlarged from some pathological cause. It is, how- 
ever, difficult to make a distinction between these two conditions, 
partly possible only by examination of microscopic sections. There- 
fore in a gross anatomical sense there is usually included under the 
term hemangioma, in a tentative way, a second variety "which is 
made up of blood lacunae, which give rise to a nodular irregularity 
in shape and a spongy consistence of the part affected [cavernous 
hemangioma]. 




Fig. 99. 
Portion of cavernous angioma of cow, seat of multiple thrombi. 



In man hsemangeiomata are represented first by the invariably 
congenital blood-red or bluish-red, sharply outlined areas of skin, 
in which the tissue of the cutis, often to the depth of the sub- 
cutaneous fat, is filled completely with thin-walled bloodvessels in 
a definitely limited area '(Hemangioma teleangiectaticum, nce- 
zus vasculosis, Hammeus, vinosus, wine mark). 

Such independent vascular tumors, caused by a disturbance of 
tissue development, are, it appears, but rarely met in animals, prob- 
ably because the pigment and hair of the skin conceals their pres- 
ence. However, Leisering observed an angioma as large as a hen's 
egg in a dog, in the subcutaneous tissue (under surface of the tail) ; 
Siedamgrotzky a similar one in a poodle, showing as a bluish-black 
area through the skin ; Bonnet a fibroangioma as large as a child's 
head with a strong connective tissue stroma in a horse, in the papil- 



Hemangioma. 



363 



lary bodies of the root of the tail. Similar teleangiectases are more 
frequently recorded as occurring in the nasal septum in the horse 
(Lupke, Hofmann, Diegendesch, et al.), appearing as superficial 
red or bluish-red, smooth, easily bleeding areas. 

The very common capillary teleangiectases in the bovine liver, 
multiple purplish-red or bluish-red spots showing through the Glis- 
sonian capsule, and appearing as finely spongy, bloody areas in 
section, are to be regarded according to the studies of Stroh as due 
to passive hyperaemia (pressure by the paunch in tympanites). 

The second type of angioma above mentioned is the cavernous 
angioma of the human liver, occurring in similar forms in the cow 
and horse. A system of blood spaces is formed in the liver, corn- 




Fig. 100. 
Portions of an angiomatous liver of a horse. 



parable to the erectile tissue of the penis or to coarse sponge, with 
cavernous passages of very irregular width and varicose, interrupted 
by projecting ledge-like bands of connective tissue. The area, recog- 
nizable from the external surface by the superficial dark red eleva- 
tions and the increased volume of the involved lobe of the liver, is 
not sharply outlined, and contains quantities of tarry blood and fre- 
quently also firm laminated clots. Between the connective tissue 
septa islets of liver structure sometimes persist. The whole appear- 
ance gives one the impression of a bunch of distended veins, dilated 



364 Tumors. 

from passive congestion, or a nodular hemorrhagic focus, rather 
than of a neoplasm. In man, however, such foci have been ob- 
served in congenital occurrences ; and Ribbert suspects as the fun- 
damental cause some developmental disturbances of the affected 
part of the liver. 

The name lymphangioma, or lymph vessel tumor, is applied to 
congenital tumors in man, which occur as independent bunches of 
lymph vessels (that is, not in direct relation with the lymph vessels 



SB© 









tfl 



** s • \ 




' * \ 



" . < 



t . 






Fig. 101. 



Cavernous angioma : a, lacuna filled with blood ; h, indurated intervascular 

connective tissue. 

of the adjacent tissues). They are especially seen in the neck, in 
the mesentery, the lips and the genital organs, sometimes not well 
defined and causing rather a diffuse swelling of the part. They are 
made up of channel-like, anastomosing, multiloculated passages 
filled with lymph, their walls of fibrous tissue lined with endothe- 
lium. 

There is only one definite and certain record of the occurrence 
of this type of tumor in animals, published by H. Markus ;* on the 

* Monatsheft f. pr. Tierheillc. Stuttgart, 1902, p. 185. 



Lymphangioma ; Sarcoma. 365 

costal, pulmonary and pericardial pleura of a horse there were found 
numerous superficial, vesicular growths from the size of a pin's head 
to that of a nut or pigeon's Qgg, some with broad surface, others 
pedunculated, exuding a serous fluid on section from the spongy 
tissue. Microscopically, they consisted of a loculated connective 
tissue framework, the spaces lined with endothelium and containing 
scattered lymph cells. The growth was entirely local, the lymph 
glands not affected. 

Schindelka observed in a cat as an anomaly, perhaps of this same 
category, a number of tumors about all the nipples, ranging in size from 
that of a hazel nut to that of a hen's egg, encircling the nipples and hang- 
ing loosely, filled, with fluid and fluctuating like a leather bottle when 
handled ; firm lymph cords, of the thickness of the little finger and varicose, 
branched out from these formations into the skin. 

Now and then large, tortuous lymph vessels filled with lymph are found 
in the horse in the heart or mesentery, which are, however, merely lymph- 
angiectases. 

Sarcomata. 

The name sarcoma ( <rdp%, flesh ; fleshy tumor, from its similarity 
to proud flesh or exuberant granulation tissue) was applied by Yir- 
chow to those connective tissue tumors which do not possess the 
definitive characteristics of a fibroma, chondroma, lipoma, etc., that 
is, which are not composed entirely of mature fibrous tissue, carti- 
lage, bone, etc., btit throughout their continuous growth are made 
up of cells of the connective tissue group persisting in their embry- 
onic characters. They are new growths whose tissue shows no 
tendency to maturation and is composed principally just as in 
embryonic life of undifferentiated mesoblastic cells and scanty in- 
tercellular substance, and which are distinguished from the simple 
connective tissue tumors particularly by their malignant character, 
their rapid and destructive growth, their tendency to recurrence 
after removal and their formation of metastases. 

The sarcomata arc classified from two standpoints: first, from 
the predominating type of the cells of the growth; and second, 
from the admixture of mature tissue with the embryonic cells. 

Many sarcomata are characterized by a special predominating 
type of cell ; and although the shape of a cell does not alone deter- 
mine the character of a tumor, the tissues of origin and the nature of 
growth being also taken into consideration, it gives the microscopic 
picttire of a tumor an individuality of importance in nomenclature, 
and characteristic because of the deficiency of fully matured types oj 



366 



Tumors. 



tissue. Those forms of sarcoma whose cells do not grow with any 
special uniformity, but rather as a motley mass of various forms in 
atypical embryonal proliferation, cannot of course be named from 
the cellular character. These instances, as a rule, represent the 
malignant form of fibroma, chondroma, osteoma or melanoma, or 
are mixed tumors ; in these cases a combined expression is used. 
The completely developed tissue forms, as it were, the framework or 
stroma, and the cells the parenchyma. 



<§?-■! 



FftfVt 






<S>. 







*V< &< 



)^/& 



l 5fi 






frilf; 









saw-* i « 



Fig. 102. 
Alveolar round cell sarcoma, from testicle (human). 



The principal types of sarcoma may be divided as follows : 
A — Cellular Sarcomata: the round cell sarcoma, spindle cell sar- 
coma, giant cell sarcoma, stellate cell sarcoma, polymorphocellular 
sarcoma. 

B — Combined Sarcomata : the fibrosarcoma, liposarcoma, chon- 
drosarcoma, osteosarcoma, myxosarcoma, myosarcoma, gliosarcoma, 
lymphosarcoma, melanosarcoma. 

In stricter application it would be well to determine precisely, as Borst 
and Diirk have urged, whether the embryonal cells were present from the 



Sarcoma. 367 

» 

beginning, and their proliferation and that of the mature types of cells 
have from the first developed side by side, or whether a simple tumor 
originally existed and later assumed a typical growth from changes in the 
cellular proliferate. In the former case the combined types of tissue may 
be indicated by the use of two nouns (as fibro-sarcoma) ; in the latter 
by the adjective prefix "sarcomatous" [the change into sarcomatous type 
may be expressed]. In the course of clinical observations, where the 
succession of various features is recognizable, such distinctions may be occa- 
sionally made ; but in purely anatomical considerations they cannot be made. 






• '^ x VV.%* / WOT. i * • ,- ,^. 



*» 









^ <=? o & ^ 















«5> 



, > ^ ^ 5- £,:*& v ^ :^ v ^** i >v. ^ 






*-6fc <*^ 



Fig. 103. 



Spindle cell sarcoma, from periosteal origin: f/, transverse section of bundle of 

spindle cells ; I), capillary blood vessel. 

The round cell sarcoma (sarcoma globocellulare) consists cither 
of cells of the appearance of lymphocytes, small round elements with 
narrow cytoplasm and granular nucleus (small cell sarcoma), or of 
large round and polymorphous cells (large cell sarcoma), closely 
packed together and with such a small amount of fibrillar intercellu- 
lar substance that the cells are but loosely attached. The tumor 
has a very soft consistence and is of a grayish to a grayish-red 
color. When the supportive tissue' enclosing the round cells is 
arranged in a reticular manner, forming a fine fibrillar meshwork, 
and the tumor has originated from one of the lymphatic structures 



368 Tumors. 

(spleen, lymph glands, bone marrow), it is known as a lympho- 
sarcoma. 

The spindle cell sarcoma (sarcoma fiisicellulare) also presents 
both small and large cellular elements and originates from ordinary- 
connective tissue. Its spindle shaped, more or less elongated cells 
contain one or more round to fusiform nuclei, are placed parallel 
to each other, arranged along the bloodvessels in bundles inter- 
twining in different directions, and are comparable to the fibro- 










V N 
















t> 



^v-J| 









Fig. 104. 

Giant cell sarcoma, from human jaw : a, capillary blood channel : b, giant cell ; 
c, sarcomatous ceils, in this specimen of spindle type. 

blasts of granulation tissue. The bloodvessels are also of em- 
bryonic type, persisting as simple endothelial channels, often distin- 
guishable from lymph spaces merely by the fact that they contain 
red blood cells. Where the intercellular fibrillar substance is more 
prominently developed the spindle cell sarcoma becomes a fibro- 
sarcoma. 

The giant cell sarcoma (sarcoma gigantocelhilare) . The pres- 
ence of numerous giant cells in a connective tissue tumor, always 
a striking feature of the microscopic sections, gives origin to the 
term giant cell sarcoma. The large polynucleated cells thus known 



Sarcoma, 369 

are usually derivatives of the marrow or periosteum where they 
occur normally (known as myeloplaxes). They differ from the 
degenerative types of giant cells (formed in tubercles and about 
foreign bodies) in the fact that their nuclei are not located about 
the periphery but are scattered well in the interior and all through 
the cell protoplasm; but all sorts of variations may be found (com- 
pletely divided or wreath-like clumping of the nuclei, giant nuclei, 
eccentric dividing forms, budding nuclei). The number of nuclei 
in one cell may reach not merely a dozen or two, but hundreds. 
The cells, whose dimensions may exceed ten to thirty times that of 
a white blood corpuscle, are irregularly rounded, their margins 
jagged, are flattened out like large fibroblasts and are often vacuo- 
lated with fat droplets. In addition to the giant cells there are 
usually numerous round and spindle shaped cells in the tumor, and 
a rich supply of capillary vessels from which blood extravasations 
are frequently found in the tissue, and which give the tumor a 
dark-red or brownish-red color. From its medullary origin the 
giant cell sarcoma is often called a myelogenous sarcoma or mye- 
loma; and when a homogeneous intercellular substance is present, 
becoming calcified and forming cartilaginous islands or bony tra- 
becula, the combined appearances are denoted by the terms osteoid 
sarcoma and osteochondrosarcoma. 

The stellate or reticular cell sarcoma (sarcoma stelloccllulare) 
is characterized by highly branched cells forming an intricate mesh- 
work, usually enclosing between their projections a mucoid, glass- 
like intercellular material, giving to the growth characteristics 
commonly indicated by the term myxosarcoma. 

The polymorphocellular sarcoma (sarcoma mixtoccllulare) is a 
name given to those connective tissue tumors whose cellular con- 
stituents follow no one cellular form, but are made up of a con- 
fused mixture of round, spindle, stellate and giant cells, or the bulk 
of whose cells are elements of variable form, irregularly polygonal, 
enclosed in a comparatively small amount of intercellular matrix. 

The morphological appearance of sarcoma cells, the size and 
polygonal shape of their cellular substance and their alveolated 
arrangement make it often very difficult to determine to which of 
the classes of sarcomata described and specially named by differ 
ent authors a given sarcomatous neoplasm should be referred. 
This difficulty and the lack of finality in our histogenic basis of 
classification arc apparent in the frequent employment of combined 
names indicating the mental uncertainty of the pathologist, as sar- 
coma carcinomatodes, or carcinoma sarcomatodes; and it is nol an 



3d 



o Tumors. 



uncommon • thing for good histologists to make use of different 
diagnostic terms to describe one and the same tumor, one perhaps 
calling it sarcoma, others endothelioma, perithelioma or alveolar 
sarcoma. This is but natural when one considers the number and 
variability* of connective tissue tumors and their combinations, the 
differences of composition which exist in different parts of one indi- 
vidual growth and the ch;. :id metaplasias which are possible, 
these features preventing any schematic and clearly defined classi- 
fication. 

The macroscopic appearances of sarcomata are naturally very 
variable on account of the many types of histological structure 
which they may present. Some are soft, others hard : their color is 
generally a grayish-white, similar to the tissue of lymph glands or 
foetal brain tissue < hence the old terms medullary sarcoma and 
encephaloid sarcoma | . They are usually rapidly growing tumors, 
some growing in nodular, nodal or lobulated forms, others as infil- 
trative growths. Their expansion not only occasions considerable 
pressure upon the surrounding :: ; nd organs, but by stretching 

the tissues they approach the surface of the organ, break through 
the mucous membrane or external skin. :r destroy the part from 
which they arise by their deeper growth. By their infiltrative 
growth and penetration between the tissues sarcomatous formations 
occasion marked enlargement in bulk and expansion of the part 
affected. Isolated tumors, reaching from five to seventeen kilograms 
in weight, and enlargements of organs of perhaps twice or three 
times the normal size, are not uncommon in sarcomatosis of the 
kidneys, liver, rectum, spleen and lymph glands. The great tendency 
to infiltration occasions laughter nodes in the vicinity of the orig- 
inal growth and leads to metastases, which are especially likely to 
follow the blood current. Penetration into blood vessels is often 
apparent to the unaided eye in c:. ; : : large veins, as those of the 
liver. The tissue increase, both in the primary and secondary 
tumors, is always due to the independent proliferation of the sar- 
coma cells, the formation of blood vessels i associated prolifera- 
tion), however, proceeding directly from the organ in which the 
sarcoma cells are distributed, apparently from a peculiar influ- 
ence exerted by the tumor cells upon the endothelium (Ribbert). 
These vessels, proliferating in association with the tumor cells, for 
the most part maintain their capillary type, often, of course, as 
wide endothelial tubes ; the frequence of haemorrhage in the sar- 
coma substance being due to the thinness of their walls. Because 
of this abnormality in the blood supply, which may not keep pace 



Sarcoma. 371 

with the rapid exuberance of the cellular growth, various retro- 
grade metamorphoses are possible, of which fatty degeneration is 
the most common. 

Nothing certain is known of the development and cause of origin 
of sarcomata. Now and again sarcomata and their combined 
growths are met following traumatism (fractures of bone > contu- 
sions and injuries to the soft parts) ; from the analogy shown by lux- 
uriant traumatic granulation tissue growth to the sarcomata, it may 
be supposed that some instances are due to lesions causing loss 
of tissue tension, and further investigation of convincing ex- 
amples would be of much interest in this line. In the second place 
sarcomata may be thought of as perhaps related in their origin with 
faults of development, both because they are common in man and 
animals in early life and because their cellular character is sugges- 
tive of embryonal conditions. 

The principal seats of primary sarcoma formation in animals 
are the bones (jaw in dogs and horses, cranial cavity in cattle), the 
lymphatic glands and spleen (dogs, cattle), and the intestine (cat- 
tle) (Frohner, Leisering, Dieckerhoff, Siedamgrotzky, Casper). 

[Of the sarcomas it may be said in a general way, to which ex- 
ceptions are not infrequent, that the spindle cell varieties more 
commonly arise from the denser types of connective tissue as the 
periosteum, fasciae, intermuscular septa and capsules or framework 
of organs ; and that the round cell forms more commonly originate 
from the softer and more cellular types of connective tissue, as the 
lymphoid structures and the intraparenchymatous intercellular con- 
nective tissue of organs. The giant cell sarcoma is practically lim- 
ited to the bone marrow, usually growing toward the ends of the 
shafts of the long bones. 

In the same comprehensive way, again with many exceptions, it 
may be expected that the round cell types are the larger, more irreg- 
ular and more infiltrative as primary growths, and of a soft fleshy 
consistence, highly vascular, and, before the blood has been washed 
out, of a red, translucent, soft fleshy appearance (paler, as above de- 
scribed, after the blood has been removed or if the growth when 
obtained from the subject is relatively freed from its blood con- 
tents) ; the spindle cell form tending in the same general and un- 
fixed manner to be smaller in size, less infiltrative, but rarely encap- 
sulated, more regular in outline and nodular or lobulated, somewhat 
firmer in consistence and of a lighter color than the round cell vnrie- 
ties. The giant cell sarcoma usually causes an expansion of the 
bone shaft, is covered with a thin and generally imperfect shell of 



2)72. Tumors. 

bone, the interior sarcomatous mass soft (sometimes almost mushy), 
deep red and hemorrhagic and bleeding freely when cut into. The 
hemorrhagic tendency is often so pronounced that the term aneu- 
rismal sarcoma has been applied to describe this feature of marked 
vascularity. 

Of the sarcomata above described by the author, the highest 
grade of malignancy from metastasis is met among the round cell 
varieties, especially the small round cell sarcoma and the alveolar 
round cell sarcoma ; spindle cell sarcomata are also decidedly metas- 
tatic in the small cell form ; the large spindle cell sarcoma being 
sometimes metastatic, but especially showing its power in this direc- 
tion by recurrence after removal (hence sometimes called recurrent 
fibroid tumor). The giant cell sarcoma is often said not to give 
rise to metastasis ; but this not strictly the case, as in man the editor 
has encountered two well-established instances of metastatic for- 
mations of this type, once from a myeloid sarcoma of the upper end 
of the tibia to one of the tarsal bones, and again from a similar 
growth in the upper end of the shaft of the femur to the pelvis]. 

Lymphomata. 

By the names lymphomata or lynipho-sarcoinata are meant pro- 
gressive proliferations of a tissue of the type of that of the lym- 
phatic glands, originating from the lymphatic structures of the 
body. Lymphatic tissue is found in the lymph glands, bone, marrow, 
spleen and thymus gland and is represented, too, by microscopically 
small developmental areas of lymphocytes widely distributed 
through the connective tissue of the system. The number and size 
of these depots and developmental foci of the leucocytes and 
lymphocytes vary considerably in different individuals, even physio- 
logically. For example, the thymus gland is often found double the 
size attributed to it as normal, and in some calves the intestinal 
lymphatic glands are so much enlarged and so confluent that the 
mucous membrane in its entire extent may approach a centimeter 
in thickness, without the possibility of speaking of this ^o-called 
lymphatismus [status lymphaticus] directly as a pathological 
condition (Johne). So, too, in calves and also in goats, hogs and 
dogs, enlargements of the lymph glands are found which are due to 
proliferation of their lymphoid tissue, and from one standpoint may 
be regarded as hyperplasias, but which assume the character of 
tumors in their progressive infiltrative extension and are very 
doubtful so far as the history of their causation is concerned. These 



Lymphoma. 



373 



growths are spoken of as lymphomatosis, progressive lymphomata, 
Hodgkin's Disease or malignant lymphosarcomatosis. The affec- 
tion manifests itself by a gradual enlargement of one group of 
lymph glands in excess of the rest. In all parts where the glands 
are palpable, as in the flexures of joints, in front and back of joints, 
along the neck, in the throat, they may be recognized as rounded 




Fig. 105. 
Urinary bladder of cow beset will) lymphomata (laid open) 



oval movable bodies, enlarged to the size of a nut or that of a fist. 
At autopsy the lymph glands of the interior of the body are also 
found changed into large nodulated masses, sometimes reaching 
the size of a human head. At first the capsules of the glands arc 
retained and, as a consequence, the nodular enlargements arc well 
defined; their consistence varies, sometimes soft, sometimes firm, 
and the surface of section has throughout a uniform grayish-white 



374 



Tumors. 



color. The minute structure of these enlarged glands corresponds 
more or less closely to that of normal ones, but differentiation into 
follicles, lymph cords and lymph sinuses is less marked, and the tis- 
sue is more uniform. The tumor mass is made up of a finely fibrillar 
or more coarsely trabecular network of connective tissue and blood 
vessels in which are uniformly distributed, in close apposition to 
each other, cells of the type of lymphocytes. In addition to the 
small rounded lymphocytes with round nuclei rich in chromatin, 
there may be found larger cells like those often met as early or 
provisional forms in the germinal centers of the follicles, and once 
and a while a few giant cells (Ribbert). Besides the proper lymph 
nodes the follicles of the intestine, pharnyx, and especially the 
lymphatic foci of the spleen, also undergo enlargement. The last- 




Fig. 106. 
Malignant lymphoma in kidney of hog. 

named organ may reach very marked excess of volume, either show- 
ing its Malpighian bodies increased to the size of a millet seed or 
a pea (follicular hyperplasia of the spleen), or the whole pulp as 
well evincing great increase of its lymphatic constituents as a 
grayish-red swollen mass (diffuse splenic hyperplasia). 

In the course of the progressive proliferation the lymphatic 
tissue passes beyond its original limits, the capsules of the lymph 
nodes are broken through and the bunches of glands coalesce into 
shapeless masses. Diffuse extension takes place, the adjacent soft 
parts becoming occupied by the penetrating lymphoma, and an infil- 
trative type of enlargement is assumed from which the glandular 
parenchymatous structures, like the liver and kidneys, may also 
become diffusely and very markedly enlarged. The infiltrating 
lymphoid tissue gives to the parenchyma of such parts a pale gray 



Lymphoma. 



375 



color, which may be either diffuse or present an irregular mottling. 
The infiltration follows along the lymph spaces of the connective 
tissue, especially along the perivascular lymph channels, and may 
lead by special local accumulations of the tumor cells to the pro- 
duction of new tumor-like nodes as well. The lymphosarcomatous 
cells, however, also penetrate into the blood vessels, and by con- 




Fi£. 107. 
Multiple lymphomata In liver of hog {general progressive lymphomatosis). 

vection may occasion metastatic nodules in various organs, especially 
in their lymphatic structures. The fact that the lymph glands in 
order of position undergo enlargement one after another, and that 
the metastases are principally located in the lymphatic structures, 
may, it is thought, bo due to chemotactic influences of related 
types of cells (Ribbert). It may be that the lymphosarcoma cells 



376 



Tumors. 



are lodged in the lymph centres having passed through the capil- 
laries, because the lymph cells present in these foci have an attrac- 
tion for them; besides, apart from such a mode, the tumor cells 
carried in the lymph stream are bound to enter the lymph glands, 
where they are filtered from the lymph and remain. According to 
Ribbert's views, progressive lymphomatosis is a true tumor forma- 
tion. The successively involved glands show the inception of the 
new formation often by well defined foci, sometimes only to be 
recognized in the peripheral sinus of the node, this arguing for 




>^ 



Lymphosarcomatosis of liver cf ccw (low power) 
Fig. 108. 



transference of the tumor element from a primary focus. By others 
it is believed that some infectious process, bacterial in nature, is 
connected, and that the microorganisms gain access to the lymph 
glands in the lymph circulation and set up proliferative processes 
in the nodes ; but as yet inoculation experiments have given no posi- 
tive evidence. [The author's statement is true; yet glandular en- 
largements, clinically regarded as belonging to Hodgkin's disease, 
have repeatedly been found to be tuberculous in nature. The 
lymphomatoses probably should be looked upon as of two types, one 



Melanoma. 377 

of which is best regarded as merely a lymphatic hyperplasia occas- 
sioned by microorganisms or toxic substances which are in some 
way brought to the lymph nodes (and some of these are tuberculous, 
the remainder probably being products of a variety of microbic and 
toxic influences). The second group may be properly referred to 
the class of the sarcomas and spoken of as lymphosarcoma and 
lymphadenoid sarcoma. The term lymphoma may be provisionally 
retained to cover the group of uncertain or indistinguishable exam- 
ples, but has no other place properly in tumor nomenclature. If 
we limit ourselves to that series of cases, to which, from their 
higher infiltrative and metastatic tendency (especially where we can 
recognize that the secondary nodules are true metastases and not 
mere hyperplasias of previously existing lymphoid foci which may 
have been induced by an original microbic or toxic cause), the 
name sarcoma may be reasonably applied. It should be added that 
lymphosarcoma is a highly malignant type of sarcoma, ranking with 
the ordinary small round cell variety in the severity of malignancy 
from metastasis. It is, of course, difficult to make the separa- 
tion in a large group of cases, but as far as possible we should 
endeavor to exclude from the term lymphosarcoma those cases in 
which enlargements manifest any appearances of infectious origin. 
Where among these there is evidence of tuberculosis of course 
the case is promptly referred to as tuberculous lymphatic hyper- 
plasia. For the rest of the cases the non-distinctive term Hodg- 
kin's disease may be employed if desired ; and it is well to keep 
clearly in mind that the affection known as lymphatic leukaemia, 
both acute and chronic, bears close relationship with the latter 
group.] 

Melanomata. 

A melanoma, melano sarcoma (chromatophoro>na) , or pig- 
mented tumor, is characterized by a black-brown or slate-gray 
color produced by the pigment cells (chromatophores) which 
constitute the growth. Normally pigment cells are found as 
specially differentiated connective tissue elements in the skin 
and choroid coat of the eye, and in some animals, as sheep, also in 
the pia mater of the brain. The melanomata take their origin 
from these cells and are therefore found most frequently in the 
skin, being especially common in horses. It is peculiar that gray 
and light colored horses, which as foals had a dark coat of hair, 
should be especially prone to these tumors ; and it may be 



37« 



Tumors. 



presumed that irregularities of their loss of pigment underlies 
the anomaly. Melanoma may, however, also occur in brown 
horses and has been seen once in a black (Hall). In most 
instances these growths develop in horses in the region of the root 
of the tail, the anus and external genitalia. In these positions 
they form nodes which protrude like boils beneath the skin, 
attaining the size of several fists and several kilograms in weight. 
Secondary nodes are formed along the lymph passages, so that 
in the cellular tissue of the pelvis there may be found whole 
chains of tumor nodes ; and by infiltrative growth the tumor 




Fig. 109. 
Section through horse's tail involved by melanoma. 



may completely invade the cutis and subcutaneous tissue, and 
cause widespread thickening and swelling. The growth is 
usually slow ; it may continue for several years as a circum- 
scribed and strictly local process, at other times being highly 
metastatic and causing an extensive generalized melanosarco- 
matosis, with secondary nodes in the lung, pleura, spleen, liver, 
kidneys, bones, musculature and elsewhere. Melanomata of the 
same nature as the above have been met also as primary growths 
in the cellular tissue near the parotid gland, in the pancreas 
(Kasewurm), intestine (Csokor), at the base of the heart (Dex- 
ler), and in the spleen. 



Melanoma. 



379 



In cattle melanomata are of less frequent occurrence. Metz 
saw two cases in white animals ; in one the tumor was situated 
in the dewlap, in the second in the pelvic cavity near the uterus. 
Hamburger found one tumor of this kind in the diaphragm ; 
Hoare removed a melanoma weighing fifteen kilograms from the 
temporal region of a brown ox. Bollinger has recorded the 
occurrence of a congenital melanoma of the size of a fist in the 
cranial cavity of a thirty-day-old calf; Wulf, a similar growth 
in the subcutaneous tissue of the ankle of a calf. In sheep 
Worseley has reported a case of melanosarcomatosis involving 






WP 



^"|iA-.® 



% 













Fig. 110. 
Microscopic section of skin of horse infiltrated with melanoma. 



the lumbar region, mammary glands, lungs and liver. In the dog 
the author has observed a melanoma springing from the gums, 
and Bruckmiiller one at the base of the brain. 

Some melanomata have a firm, rather dry appearance ; others 
are found of soft consistence. The cut surface is uniformly 
dark, or sepia-brown or slaty ; when handled the fingers are 
soiled as if with shoe-blacking. 

Microscopically the pigment is found in the form of brown- 
ish black granules, which are distributed in the fluids of the 



380 Tumors. 

tumor and within the cells. The latter elements are seen as 
variably shaped, irregularly rounded, fusiform and branched 
cells, their cytoplasm usually so thickly loaded with the dark 
brown granules that the nucleus is obscured ; at places, however, 
they may be found entirely free from pigment. The cells are 
usually so closely packed together that their outlines cannot 
always be differentiated. The tumor tissue is very clearly 
denned from the rest of the tissues, into the lymph spaces of 
which the neoplasm can be seen to be extending its way, afford- 
ing an excellent demonstration under the microscope of the 
mode of propagation of these growths. The cells are so easily 
loosened in the softer specimens that the tumor mass may stand 
out like thick pultaceous material; Csokor has observed in the 
case of a horse with the intestinal mucous membrane (colon) 
the seat of melanoma, the discharge of black fecal matter ; and 
Bollinger, Bruckmiiller and Semmer have found the pigment 
granules in the blood (melansemia). 

The pigment material known as melanin, certainly does not 
come from the blood (iron free), but is formed by a specific 
activity of the chromatophorous cells, as Berdez and Nencki 
have shown ; the important proportion of sulphur in its compo- 
sition suggests that it is a derivative of albuminous bodies. 

The origin of melanomata is necessarily in some way related 
to developmental disturbances which give rise to excessive pro- 
duction or misplacement of pigment cells; their occurrence as 
congenital tumors and the fact that in man the growths are 
known to frequently take their start from congenital pigment 
moles of the skin, are evidence in favor of such a view. 

The malignancy of these growths is not uniform ; as above 
stated, some may remain in their primary situation for years 
without appreciable enlargement, and may not recur when re- 
moved, but others, especially the softer forms, spread rapidly and 
widely and give rise to great numbers of secondary nodes. [The 
melanotic sarcoma of man, most commonly met in the eye, is ex- 
tremely malignant, ranking probably first of all in the list of sar- 
comata in this respect.] 

Endotheliomata, Peritheliomata, Cholesteatomata. 

By the term endothelioma is meant a tumor which is com- 
posed of endothelial cells of connective tissue derivation, espe- 
cially those of blood vessels and lymph vessels, as well as those 



Endothelioma. 381 

of the dura mater of the brain and spinal cord. Endotheliomata 
in their structure stand relatively midway between the atypical 
connective tissue growths and epithelial tumors, and resemble now 
one and now the other of these so closely as to make their distinc- 
tion from sarcomata or carcinomata often practically impossible 
where only single bits of the growths are subjected to micro- 
scopic examination. They differ from cancers in the history of 
their development, the latter taking their origin from epithelium, 







Fig. 111. 

Endothelioma of lymphgland (human) : a, lymphoid tissue of gland ; b, leucocytes 
in nearly obliterated lymph-sinus ; c, endothelial cells proliferated from lining 
of lymph-sinus. 

either ectodermal or entodermal, while the true endotheliomata 
are of mesoblastic origin. It is more difficult to define them 
from sarcomata, the cells of the latter being also derived from the 
middle germinal layer ; and for this reason some authors speak 
of them as endothelial sarcomata. (The layer of so-called endo- 
thelial cells lining the largo serous cavities of the body, the coelo- 
matous lining, is to be regarded as epithelial and the tumors 
which arise from these cells are therefore to be classed as 
cancers.) 



382 Tumors. 

The cells of an endothelioma present the same polygonal, 
flattened, fusiform and polyhedral forms as the fibroblasts and 
angioblasts, the cells of the blood and lymph vessels being, in 
fact, formed originally of the same material. In the tumors they 
are arranged as scales, or in cylindrical cords or in hollow tubu- 
lar manner so as to form a network with thickened nodal points, 
and are supported by a vascular stroma. The microscopic appear- 
ance is therefore very like that of an alveolar sarcoma or carci- 
noma : sometimes the arrangement of the cells in lamellae may be 
concentric like the tunic of an onion. . 

Those endotheliomata which take their origin from the outer 
coat (adventitia) of the bloodvessels (from the perithelial cells) 
and are recognized as forming mantles of tumor cells about the 
blood vessel and its branches, are generally spoken of as pcri- 
thcliomata. 

Retrograde changes which occur in endotheliomata may give 
an unusual appearance to some forms, in consequence of which 
special names are applied. As an example the cylindrical cords 
may undergo hyaline degeneration of their endothelial cells, be 
transformed into shining homogeneous structures, standing out 
conspicuously in transverse section like hyaline, concentrically 
laminated balls or masses: this appearance has led to their being 
called cylindromata. In other instances calcareous deposits (in 
the form of globules, needles and club-shaped masses) occur in 
the structure of the growth, giving a grittiness to the tumor in 
section and making the cut surface rough and sandy ; these are 
especially met in the brain and are known as psammomata [acer- 
vuloma, sand tumor). The endotheliomata which develop from 
the choroid plexus of the brain are always richly infiltrated with 
cholesterin deposits, and are called in a superficial way cJwles- 
teatomata. 

However these changes or depositions which give occasion for the special 
names indicated are not absolutely restricted to one particular type of tumor. 
In the collection of lime and cholesterin it must be kept in mind that the 
cells of the neoplasm are preserving qualities of the cells from which they 
had their derivation, for brain sand and cholesterin are found normally also 
in the pineal gland and in the choroid tissue. True epithelial tumors, how- 
ever, which occur in the cranial cavity and are referable to inclusions of 
epidermoidal rests usual]}- contain cholesterin, and it is also met in dermoid 
cysts or epidermoid cysts of the subcutaneous tissue ; these types requiring 
the acceptance of a further class, the epithelial cholesteatomata. 

Contributions recording the occurrence of endotheliomata in 
animals are very meagrely found in literature. Dexler met in a 



Cholesteatoma; Papilloma. 383 

dog an endothelioma originating from the spinal dura mater; 
Kiinnemann a psammoma of the cranial dura mater about the 
size of a duck's egg, overlying the anterior part of the brain in 
a cow. Cholesteatomata have been found rather frequently in 
the lateral ventricles in the horse ; met in this location they are 
rounded, reniform nodes, varying in size from that of a lentil to 
that of an egg, usually occurring bilaterally, a tumor suspended 
from the choroid plexus in each ventricle. The surface is smooth 
and shining, sometimes granular; the color white, gray or grayish- 
yellow ; the consistence about that of the liver, the cut surface 
slightly gritty and the cholesterin recognizable in tiny opalescent, 
shiny spots. Microscopically these tumors are made up of blood- 
vessels, a loose connective tissue stroma and the endothelial ele- 
ments, which have grown from the bloodvessel wall ; between 
these cells, in the' vessel walls and in the widened lumina of the 
latter the cholesterin may be seen in the form of superimposed, 
step-like plates with the borders broken out. In addition round 
cells and pigmentary deposits may also be found. (Cornil and 
Ranvier speak of the tumors in question as angiolithic sarco- 
mata ; Casper employs the term haemangiosarcoma perivascu- 
losum). 

[The position taken by the author in excluding from the 
endotheliomata tumors originating from endothelium of the 
large serous sacs, is not generally accepted ; and endotheliomata 
of the pleura especially have been frequently described. 

Endotheliomata as a rule are slowly growing tumors and 
although capable of metastasis are generally not marked by 
many secondary formations. This, however, in some individual 
examples is quite reversed and high metastatic malignancy is 
manifested. So, too, in most cases they are not recurrent after 
extirpation, but here again exceptions must be recognized. 
They may occur as multiple primary growths. The subdivisions 
above mentioned, cylindroma, cholesteatoma and psammoma, 
are as a rule merely local growths, and are among' the least 
metastatic forms of endotheliomata.] 

Papillomata. 

The name papilloma is applied as a comprehensive, even if 
not well chosen, term for fibroepithelial neoplasms which occur 
on the surface of the skin and mucous membranes in the Form 
of warty, conical, coralline, villous or nodular proliferations of 



3§4 



Tumors. 



the papillae and their overlying epithelium. The physiological 
prototype of this combination of tissue and its source of develop- 
ment are in fact the epithelial-covered papillae of the skin, but 
in their pathological proliferation the quantitive relations be- 
tween the two forms of tissue are very irregular. In some 
tumors the connective tissue growth is so predominant that the 
tumor practically consists of thick clumps of this tissue covered 
only by a thin layer of epithelium rather stretched over the mass 




Fig. 112. 
Cutaneous papillomatosis of beef. 

than growing with it (for which reason some authors prefer to 
speak of such a specimen as fibroma papillare). the superficial 
papillary structure being only recognizable under the micro- 
scope. In other instances the fibrous tissue of the base of the 
tumor sends out long branched villous processes, or may undergo 
changes which give it a soft, cedematous or very vascular appear- 
ance ; and again the keratous epithelium may form so thick a 
layer as to throw the connective tissue substructure into insig- 
nificance. Different types of these fibroepithelial autoblastomata 
may be distinguished by taking such features into consideration, 



Papilloma. 



385 



On the skin and mucous membranes covered with squamous 
epithelium they occur as rounded projections, sometimes only 
as large as a pea or nut {warts, verruca;), simple local hyper- 
plasias of the papillary body with smooth epidermal covering ; or 
they sometimes occur in clumps, like grapes, as cauliflower 
tumors of the size of a fist (papilloma tuberosum, polyposum, coral- 
liforme), with superficial subdivisions, provided with broad 










'■■&■ 



mm. 3m 




Fig. 113. 
Section of papilloma of cow 



peduncles or hanging suspended by a thin stretched-out pedicle ; 
or again as thread-like or bristle-like projections (papilloma fHi- 
forme). 

Under the microscope, varying with these external shapes 
of the growth, the connective tissue, which is made up merely 
of spindle cells and fibrils with bloodvessels, may be seen as 
papillae of varying length and thickness and of all sorts of 
shapes, with knotted and clubbed branches and secondary point- 
ed projections; and the epiderm in a single or multiple layer 
extends over this, following the depressions and clefts, in which 



3 86 



Tumors. 



the epithelium may become keratosed and formed into concen- 
trically laminated arrangements (horny pearls). 

Sometimes these papillomata occur congenitally (two cases 
of the kind in question fully described by Pirl and Trolldenier* 




iii\ 



I 



fj-KvSjf, 











■H 



sip 

. w ^.t;;^. , aI lir?» ' -1'^ 7 



/V-1t 



^V'fe v-^s^riv y-r^^z 



Fig. 114. 

Papilloma coralliforme in gullet of cow. (The oesophagus has been everted and 
the mucous surface exposed ; the partly smooth appearance is due to the fact 
that a piece of wood has been forced into the lumen of the tube turned in- 
side out.) (Photograph.) 



in foals), probably due to traumatic intrauterine lesions of 
the skin caused by amniotic threads, By some authors an infec- 



* Monatsheft f. p. Tierheilk, 1903. 



Papilloma. 



387 



tious cause is suspected for certain forms of papillomata because 
the affection often appears in a number of animals at the same 
time in one stable in wide distribution over the cutaneous sur- 
face ; development after chronic inflammatory irritation of the 
skin has also been observed. Especially in the skin of the udder 
of the cow and in young cattle, but also in other positions in this 
species there often develop great numbers of warty and nodular 
papillomata which may weigh en masse many pounds. These 
superficially divided growths, which are of course exposed to 
traumatic influences and contamination 
with foul pus, are apt to become mal- 
odorous from maceration of the desqua- 
mated epiderm retained in the depres- 
sions ; they often become cedematous 
and swollen, and may become more or 
less suppurative and putrefactive from 
the influence of microorganisms, which 
may have gained access into these 
parts. In similar manner the papillo- 
mata frequently developing in the frog 
of the horse's hoof (known as hoof 
cancer or frog cancer) are apt to break 
down into a foul-smelling mass because 
of incomplete keratinization of the 
epithelial surface layer and contact with 
all sorts of germs and putrid material 
(dung, foul pus). 

A favorite location for these tumors 
is the oesophagus of cattle, where the 
papillae project into the lumen of the 
tube either as thorn-like, bristle-like or 
brush-like prominences, or as circumscribed villous or coralline 
growths, or as firm nodular bunches ; the passage of food, es- 
pecially the return of the cud (in ruminants) being more or 
less interfered with. Papillomata often occur also in the psalter 
of cattle as berry-like, slightly cedematous, swollen-looking 
growths, ranging in size from the millet seed size normal to the 
papillae of the part, to pendant rosette-like bunches of projections 
half the length of the finger, club-shaped and covered smoothly 
with epithelium. In dogs the lips, buccal cavity, foreskin and 
anus are the principal sites of papillomata. 




Fig. 115. 

Congenita] papilloma of pinna 
of colt. (After Troll- 
denier.) 



388 Tumors. 

In the urinary and gall bladders of cattle, in the former also 
of horses, dogs and swine, papillary mucous membrane prolifera- 
tions occur, usually projecting as long villous, highly branched 
growths with a common pedicle into the cavity of the viscus, like 
the tentacles of a polyp (papilloma polyposum) ; they are usually 
very soft, succulent, their connective tissue cedematous and per- 
haps actually myxomatous (papilloma polyposum myxomatodes) , 
or in other cases the seat of a cellular infiltration and presenting 
evidence of inflammatory involvement. Inflammatory changes 
in the last named situations are so frequently accompanied by 
mucous membrane proliferations that some causal relationship 
may be assumed and the hyperplasia of the mucous membrane 
regarded as a sequel to a productive inflammation (Zellhuber). 

Where the epithelium of the papillary growth of the skin is 
not desquamated in scales, but in its active proliferation forms 
thicker and thicker horny layers, there is produced a hard body 
which continually grows more and more prominent and acquires 
the form of a horn-like outgrowth, a cutaneous horn (cornu cuta- 
neum). These structures are very frequently seen in cattle, 
especially in range cattle, occasionally attaining a length of half 
a meter, growing from the forehead or neck, or as a short 
conical horn from the skin of the udder. Now and then large 
spirally curved cutaneous horns are seen in goats in the thoracic 
and abdominal walls; in sheep in the ear and back; in horses and 
dogs as small claw-like horns in the ear and in other parts of the 
body. (For fuller description see Casper, Pathol, d. Geschwiilste 
b. Tieren, Wiesbaden, 1899; Kitt, Spez. pathol. Anatomie, II. Aufl., 
Stuttgart, 1 901.) 

Papillomata and cutaneous horns are regarded as benign, non- 
recurrent, persistently local new growths ; they manifest an unfavor- 
able tendency only from their size and situation. 

Adenoma. 

An adenoma, or [epithelial] glandular tumor, is a prolif- 
eration of glandular tissue, . with reproduction of its structural 
type, in the form of a tumor. Epithelium and a vascular con- 
nective tissue stroma in definite structural relations constitute 
glands, and the two forms of tissue in common contribute to the 
formation of the adenoma. Whether the epithelium was the 
primary proliferating element and, as Borst believes, the con- 
nective tissue cells took a relatively secondary part because 



Adenoma. 



389 



of their tactile sensibility, is an open question. In some adeno- 
mata the reverse is apparently the case, the connective tissue 
proliferation apparently being the major feature, in its prolifera- 
tion causing expansion of the surfaces of the gland lumina and 
thus affording space for the epithelial gland lining to develop. 
Both tissues proliferate side by side in mutual interdependence 
in the production of gland tissue. 

There are as many varieties of adenoma as there are different 
glands in the animal body, and as the tumor invariably takes its 
origin from a gland it always represents a histological copy of 
the particular gland in question. The growth has, too, in all 
instances the same type of epithelium which characterized the 
original gland, and the same kind of connective tissue stroma is 




Fig 110. 

Adenoma, of size of human head, of the gall ducts in the liver of cow ; 

(cut surface). 



preserved in more or less precise simulation of the structure 
peculiar to the parent gland. Corresponding to the different 
glands these tumors may be divided into major types of tubular, 
alveolar and follicular adenomata; and depending upon their 
origin it is customary to speak of them as sweat-gland, seba- 
ceous, hepatic, salivary, renal and other adenomata. 

In this pathological proliferation of the glandular tissue there 
occur, however, manifold modifications and abnormal features. 
The epithelium, although generally exhibiting the same structure 
and even secretory function as the original type, is often increased 



390 



Tumors. 



in size or may be present in a greater number of layers, and its 
secretion may be of a degenerative character (for example, from 
the assumption of mucoid change by the adenomatous cells or 
their destruction by excessive fat production). The connective 
tissue, which in direct limiting relations to the epithelium forms 
its tunica propria and in tabulated types of gland tissue forms a 
meshwork of septa, is often developed in special excess, forming 
densely fibrous sclerotic trabecula which embrace the glandu- 
lar ducts in compact circular investing bands (adenofibroma 
pericanalicular - e) or form club-shaped or finger-like projections, 
stretching the adenomatous lumina, increasing the surface of 
the glandular canals and extending into the latter as villous 
papillae (adeuofibroma intracanaliculare t adenoma papilliferum). 




Fig. 117. 
Adenoma flayum of liver of cow. 



The tubular or vesicular spaces of the adenoma, by continu- 
ous and progressive formation of hollow buds lined with epi- 
thelium, become more and more branched and more irregular than 
in the normal gland; and by this intricate projection of epithelial- 
covered connective tissue processes into their interior become 
changed into tortuous passages and openings, which may become 
quite large. The cut surface of an adenoma may in this way 
come to closely resemble a section through a head of cabbage, 
in which spaces are to be seen between the layers of leaves. As 
these adenomata are completely isolated new growths and their 



Adenoma. 391 

canalicular systems are in no way in communication with the 
emerging ducts of the normal glands, an accumulation of secre- 
tory material and desquamated epithelial cells is likely to be 
retained in their passages and spaces ; thus in an adenoma of 
the mammary gland milk is found as a pathological product ; in 
follicular adenomata of the thyroid, masses of colloid matter ; in 
adenomata of mucous glands, mucin. As a result of the reten- 
tion of such material the walls of the canals and alveoli become 
stretched, and this feature, together with continuous enlargement 
of their surfaces from increase of the epithelial lining and the 
connective tissue framework, may make the distended cavities 
visible to the naked eye. To tumors thus altered and containing 
cavities filled with fluid the term cystadenoma is applied ; and 
where villous projections of the lining membranes extend into 
the cavities the growth is known as cystadenoma papilliferum 
phylloides. 

The growing vascular connective tissue of the adenomatous 
structure is sometimes the seat of haemorrhagic effusions or 
cedematous swelling, due to passive congestion and transudation 
caused by kinking of the folds and villi projecting into the 
cysts. Other regressive changes, as fatty degeneration or coagu- 
lation necrosis, may also be observed. In some instances the 
stroma of the tumor is a tissue very rich in cells and of a 
reticular structure resembling a sarcoma or myxoma {adeno sarcoma, 
adenomyxoma, adenoma sarcomatodes, my. romat odes') . 

Finally glandular tumors, which in typical cases are usually 
distinctly limited from the organ in which they are situated, 
may become atypical and send out infiltrating processes into the 
surrounding tissue, penetrating into the lymph vessels and 
bloodvessels and thus assume the character of a malignant fibro- 
epithelial growth. These forms are known by the names adenoma 
destruens, adenocarcinoma [malignant adenoma]. 

Two points may be considered in attempting an explanation 
of the aetiology of adenomata. The definitely circumscribed 
nodular adenomata which develop in or close to parenchymatous 
organs are doubtless of foetal origin, coming from misplaced, 
independently developing parts of a gland. Those growing as 
single or multiple tumors from mucous surfaces, sometimes 
occupying extensive areas of the mucous membrane, often show 
in themselves, just as the neighboring parts of the membrane 
may also show, evidences of chronic inflammatory change, recog- 
nizable by cellular infiltration and by giving rise to a mixed secre 



392 Tumors. 

tory and exudative type of product. These peculiarities as well 
as the clinical course of such cases, suggestive of their origin as 
direct sequences of chronic inflammatory processes, force the 
conclusion that injuries capable of causing inflammation may 
either directly or indirectly (disturbance of tissue tension) give 
origin to adenoma production. Mucous membrane and glandu- 
lar vegetations of this type are usually spoken of as glandular 
hyperplasias or mucous membrane polyps. It should be recog- 
nized, however, that such superficially situated adenomata may 
become inflamed secondarily, from their coming in contact with 
irritants. * 

The most frequent type of adenomata occurring in animals 
are those of the sebaceous and sweat glands (adenoma seba- 
ceum, sudoriparum) in the skin of the dog; among thern particu- 
larly growths originating from the perianal glands, presenting 
rounded, nodular and lobulated forms, of a reddish yellow or light 
yellow color and giving off a fatty, greasy fluid (a number of 
descriptions of Siedamgrotzky, Lienaux, Werner). True ade- 
nomata of the liver are also comparatively common in cattle and 
sheep (Bollinger, Martin, Siedamgrotzky, Johne, personal obser- 
vations) as sharply defined tumors, surrounded by a connective 
tissue capsule, situated in the midst of the hepatic tissue. These 
may sometimes be found as large as a human head, composed 
of liver cells and delicate cob-web like connective tissue septa. 
They are usually very striking because of their bile-stained yel- 
low to green hue. Similar to these there also occur in the liver 
gall-duct tumors, with dense fibrous stroma, having, in conse- 
quence, a firm consistency and appearing as light yellow nodular 
deposits ranging in size from that of a potato to that of a human 
head. The mammary gland in dogs is another frequent site for 
cystadenomata and combined adenofibromata or for transitional 
forms becoming cancerous. In the lungs adenomata of nodular 
form may originate from the bronchial mucous glands, ob&erved 
in sheep (A. Eber) and horse. 

Although in man mucous membrane polyps occur quite fre- 
quently in the nose, such growths are more uncommon in animals ; 
in the horse they are met hanging into the naso-pharynx, hyper- 
plasias perhaps as large as a fist, lobulated, elongated, slippery and 
of mucoid consistence, composed of soft mucous membrane tissue. 
There is difficulty in trying to accurately define thyroid adenomata. 
The colloid secreting epithelium of this organ in its proliferation 
sometimes gives rise to a general enlargement of the gland, the con- 



Adenoma. 393 

dition known as goitre (struma) ; and sometimes leads to nodular 
formations which originate from isolated and independently growing 
cellular foci and are called adenomata, cystadenomata, or adenocar- 
cinomata, but which are usually accompanied by diffuse enlargement 
of the rest of the parenchyma of the organ. In the same way pro- 
liferation of the glandular tissue of the ovary and testicle is usually 
diffuse, and the distinction detween hypertrophy and true tumor 
formation is difficult here as well as in the previous example. The 
cells are usually of an indifferent type and can scarcely be distin- 
guished from sarcoma cells. In these cases the terms ovarioblastoma 
or orchidoblastoma are convenient names, according to the organ 
involved. They may be seen as solid growths or with cyst forma- 
tion associated, the whole organ involved, the tumors reaching enor- 
mous size, weighing perhaps ten or fifteen kilograms and often at- 
taining the dimensions of a human head or even twice that of the 
full stomach of a horse (in horses, cattle, sheep). 

In the kidneys true adenomata of the uriniferous tubules have 
never been observed. The tissue proliferations which develop here 
in the form of tumors, as a rule are of the destructive adenocarcino- 
matous type and convert the organ into a shapeless, soft material 
which may break through the capsule. This substance is sometimes 
as soft as marrow, gray to brownish-red in color, and is made up of 
large canals lined by cylindrical epithelium. In other cases the 
growth is combined with sarcoma and possibly also with muscle 
fibres and constitutes an adeno-rhabdomyomatous sarcoma (Johne). 
[Some of the tumors described as renal adenomata are in real- 
ity hypernephromata (v. p. 397) ; although the latter growths, which 
occur in the kidney as their most frequent seat, are ordinarily easily 
distinguishable. In man there occasionally are seen in sections of 
kidneys small isolated foci of tubular structure, with the tubules 
either small and compressed or at places distended into cystic spaces. 
In the latter papillary proliferations may be found projecting; the 
whole appearance corresponding with the adenoma papilliferum 
above described. In these cases as a rule the foci are small, perhaps 
microscopic, and the general picture of the structures suggests their 
isolation from the rest of the tissue by an inflammatory change. 
Rarely larger nodules of this character are met, to which we cannot 
refrain from applying the term adenoma. 

The prognosis of the tumors of the adenomatous group is funda- 
mentally favorable; the true adenomata being entirely free from any 
tendency to infiltrate or to give rise to metastasis. Such growths 
are harmful merely from their local influences. The variety above 



394 Tumors. 

mentioned as destructive or malignant adenoma or adenocarcinoma 
is essentially cancerous in its nature and is malignant both by local 
extension and by metastasis. Any adenoma may be regarded with 
suspicion and dealt with accordingly, when it is recalled that it is not 
very uncommon for these growths to lose their purely adenomatous 
character and become changed into adenocarcinomata.] 

Carcinomata. 

A carcinoma or cancer is a malignant new growth composed of 
epithelium and connective tissue, characterized by a persistent and 
progressive penetration of its epithelial elements into the underlying 
tissues. The cancers always originate from epithelium, either surface 
epithelium or the glandular epithelial cells of functionating organs, 
or from islets of epithelial cells formed in fcetal life and occurring 
in unusual situations. They may also take their origin from pre- 
viously existing papillomata, adenomata and cystomata, these having 
from unknown cause assumed a proliferation of their epithelial cells 
with departure from their ordinary forms and boundaries. 

The proliferating epithelium forming the cancerous parenchyma 
or body of the cancer behaves as a foreign intruder; it assumes 
an independent status by no longer remaining confined to the surface 
which it previously covered, breaking through its normal limiting 
structures and playing the part of epithelial cells which have be- 
come practically parasitic. These cells, derivatives of previously 
existing epithelium, by their penetrative growth and active multi- 
plication usually form in the deeper structures solid cords or duct- 
like processes which branch like the roots of a tree and are contin- 
ually sending out new projections into the tissue. These retain- 
ing their continuity with each other result in forming a network 
or meshwork [of epithelial character throughout the invaded 
tissue] varying in its density and with irregular nodal points 
(Ribbert). This net-like and corded arrangement of the epithelial 
roots is due to the fact that the cells in their penetration follow the 
lines of least resistance and therefore penetrate the lumen of the 
lymph passages, come to completely fill them with their growth and 
therefore to assume their shape. After occupying all the lymph 
spaces of the connective tissue the epithelial roots may penetrate 
into the tissue itself in such numbers as to practically constitute a 
diffuse infiltration (Ribbert). 

In microscopic sections the continuity of the cords is not entirely appre- 
ciated, as each sectional layer, of course, contains only segments of them. 



Cancer. 395 

»t 
In serial sections or in plastic reconstruction of the general tumor-picture 
by means of the methods of planar modeling, one may always convince 
himself of the interconnection of all the epithelial cords (Diirk). 

The connective tissue of the organ in which the epithelial cells 
are in active cancerous proliferation, does not, however, act in a 
purely passive manner, as a tissue shoved aside and compressed by 
the epithelial growth ; but reacts by an inflammatory change which 
in its chronic course leads to the production of a connective tissue 
hyperplasia. The epithelial masses act precisely like foreign bodies, 
attract leucocytes to them by chemotaxis, the latter cells collecting 
about the margins of the epithelium just as in a demarcating inflam- 
mation and sometimes producing a marked cellular infiltration of the 
connective tissue. At the same time the fixed connective tissue cells 
proliferate and form a fibrous stroma (framework of the cancer) 
of varying texture, containing young bloodvessels and enclosing epi- 
thelial nests. 

The distinction from the typical fibroepithelial tumors [adenoma, 
papilloma] lies in the fact that in the latter the epithelium and 
connective tissue are united in common growth to form a tissue com- 
plex, a compound tumor basis; while in cancer in reality only the 
epithelium is the basic tumor element, and the connective tissue 
growing along with it is the result of a productive inflammation and 
belongs properly to the organ in which the cancer is located. The 
cancer stroma therefore is but the interstitial tissue of the affected 
organ, involved by inflammation. The epithelial elements of the 
cancer develop in the organ in which the tumor originally (prim- 
arily) grew, from cells, it is true, already present therein; but the 
epithelial cells of the organ are not uniformly changed into cancer 
cells, do not all take part in the tumor construction. The growth 
and extension of the latter involves invariably a fixed group of cells 
acting as the germinal elements of the tumor, toward the multipli- 
cation of which the other epithelial cells remain passive. 

The microscopic studies of Ribbert have furnished a number of 
considerations which concern the histological production of the pri- 
mary stage of this type of tumor, the start of the cancer formation. 
Ribbert refers the origin of the growth to an isolation from the cel- 
lular union in an organ of individual epithelial cells or a group of 
cells, as an epithelial ingrowth, a separated bit of epiderm, or a 
lobule of a gland ; this subsequently assuming independent prolifer- 
ation. This isolation from physiological connection is usually 
brought about, as Ribbert recognized in microscopic sections in the 



396 Tumors. 

initial stages of skin cancers, by the intrusion of connective tissue, 
stimulated to proliferation by inflammation, between the epithelial 
cells. In other words, according to Ribbert cancers always start on 
a base of chronically inflamed tissue. The epithelial cells do not 
make the initial penetration into unaltered connective tissue ; the 
primary change being the inception of the inflammatory prolifera- 
tion of the subepithelial connective tissue, which raises the epithe- 
lium and, as the proliferating connective tissue elements invade the 
deeper epithelial layers and destroy the intercellular' cement, 
separates isolated cells from their proper relations and thus mis- 
places them. The isolated epithelium, now situated in the midst 
of the connective tissue and sufficiently nourished by it, begins 
to multiply; and, being prevented from growing upward toward 
the surface of the skin or mucous membrane, and its relations with 
the general epithelial tissue, its nerves and normal substratum 
(papillary layer) being destroyed, it must necessarily penetrate 
irregularly into the tissues along the course of the lymph spaces. 
Thus it comes to force its radicles ( and cords in every direction 
and to form the beginning of the cancer. 

As a matter of fact cancers do occur with frequence in places 
where for some time previously inflammatory irritation has existed. 
In man, for example, cancer of the lip is especially likely to be met 
in persons who smoke pipes habitually, and, too, just in the corner 
of the mouth which is always exposed to irritation from the juices 
from the pipe. The influence of soot as an irritant capable of in- 
ducing cancer is well seen in chimney-sweeps (chimney sweep's can- 
cer) ; and that of parafflne has become well known among the em- 
ployees of parafflne factories as causing epidermoidal proliferations 
(parafiine cancer of the hands). A. Sticker has called attention to 
several examples which indicate a causative relation of external 
influences upon the establishment of cancer, as the occurrence of 
skin cancer in cattle after branding (Mac Fadyan), and beneath the 
chin in swine from chaffing (Eggeling). Possibly the frequence of 
cancer of the anus of dogs has some connection with external inju- 
ries (from the animal scraping the anal region along the ground, so- 
called "sleigh-driving"). 

The origin of cancer should not, therefore, be attributed to any 
one cause, as a definite cancer parasite or an infectious agent, but 
may be determined from any influence (traumatic, chemical, infec- 
tious) which occasions chronic inflammation and because of which, 
as a result of the inflammatory process, an isolation of the living 



Cancer. 397 

epithelial cells, retaining their power of proliferation, occurs. It is 
of course true that inflammations of surfaces covered by epithelium 
and epithelial organs are frequently seen without resultant cancer 
production, even though it may be presumed that isolations of 
epithelial cells may often obtain in connection with these processes. 
But, as Ribbert insists in case of such exceptions, much depends 
upon the length of time over which the inflammation extends. In 
acute inflammations the epithelium is apt to be injured, and even if 
isolated cells be misplaced in the subjacent tissues the process is of 
too short duration to allow the cells to accommodate themselves to 
their new surroundings; they therefore perish (Ribbert). In the 
same way as an inflammatory connective tissue production, epithe- 
lial cells may in papillary and polypous new growths be cut off and 
isolated by the proliferation of the stroma, or whole cores or 
bunches of them ; and thus a primarily benign tumor may be con- 
verted into a malignant one by the progressive growth of such 
cells into the underlying tissues. The change of fibroepithelial 
growths which for years have been of simple type into destructive 
cancers is a well authenticated observation in human medicine. 
Finally, epithelial misplacements, which may accidentally be caused 
in. fcetal life in the processes of arrangement of the various tissues, 
in the formation of folds and cavities which are taking place 
among the tissues in the construction of the various organs, may 
furnish the original substance for a subsequent cancer. 

A good example of this is afforded by the nodular growths met in the 
human kidney cortex, originating from misplaced adrenal tissue. They are 
met as single or multiple growths, well denned ; and sometimes destroy the 
kidney, penetrate into the blood vessels, and give rise to fatal metastasis. 
These nodes are of a yellowish color from the fat which they' contain, and 
under the microscope are seen to be made up of cords of cells arranged 
in parallel lines along the blood vessels, and resembling in their appearance 
the epithelium of the suprarenal bodies (hypernephroma, adrenal cancer). 
LThese growths are also met with not very infrequently in the kidneys of 
cattle and occasionally in hogs ; they are not confined to the kidney, but 
may be found in any of the structures near the adrenals or in the adrenals 
themselves, where they may either represent foetal rests, or may have started 
from isolated parts or inclusions of the tissue of the organ caused by inflam- 
matory separations.] 

Ribbert's attempted explanation of the genesis of cancer is not 
as yet accepted by many pathologists. Inflammatory changes arc 
often not demonstrable at the places of origin of cancers; and sonic 
authors do not believe that the atypical proliferation of the epithe- 
lium is a result of the invasive growth of the connective tissue but 



398 Tumors. 

that some other as yet unknown causes underlie the irregular pro- 
gressive proliferation which these cells manifest (in other words, 
that the epithelial multiplication is the primary process) : and search 
for some kind of infectious agent is not as yet abandoned. The 
occasional endemic occurrence of cancer (also observed by Eggel- 
ing in hogs in a certain locality) and isolated cases which suggest 
the transmissibility of certain forms of cancer continue to keep the 
question of the infectiousness of cancer in discussion. A. Sticker, 
for example, has called attention to a dog which for a long time 
had been in the habit of lying by the bed of a man suffering from 
cancer of the stomach and ate all sorts of material which the man 
had vomited, and which became affected by a general carcinomato- 
sis (lungs, liver, omental sac. but not the alimentary canal). This 
may have been a mere coincidence, but the possibility of an sero- 
logical relationship between the two cases cannot be entirely ig- 
nored. ( Cf . p. 334.^ Experimental attempts to prove an infectious 
nature as existing in these growths (inoculation and feeding ex- 
periments) have hitherto always failed. Trasbot obtained no posi- 
tive result from hundreds of such attempts ; Duplay and Cazin 
failed in over one hundred and twenty experiments in dogs and rats ; 
Gratia and Lienaux, Cadiot and Gilbert had no more success in 
numerous attempts to transmit these tumors, employing all sorts 
of methods of inoculation (from dog to dog. from man to dog). 
The transplantation of certain forms of cancer in rats and mice has 
alone succeeded (Hanau, Moraus, C. O. Jensen ) ; but the methods 
employed do not indicate that an infectious agent was operative) 
but rather that the cells of the cancer used in the experiment were 
capable of multiplying if placed in uninjured condition in a new 
specifically similar soil ( i. e., transplanted to the same species of 
animal as that from which derived ) , and of continuous develop- 
ment into an independently growing tumor tissue in their practically 
parasitic colonization and multiplication, (cf. Definition of tumors 
p. 325.) [Transplantation of cancers in animals has invariably 
shown that success is to be expected only when the animal to which 
the tumor is transplanted is of the same species as that from which 
it was derived, even varieties of the same species making the result 
doubtful. In this country Leo Loeb, Gaylord, Herzog and others 
have carried various cancerous growths or mixed cancers through a 
number of generations in rats and mice. In these experiments actual 
portions of the living growth (bits may retain life for some hours 
when kept in moderate refrigeration after removal from the origi- 
nal animal) must be introduced into the experiment animals and 



Cancer. 399 

filtered extracts are not followed by success. Ehrlich {Berlin. 
Klin. Woehenschr., No. 28, 1905; No. 2, 1906) and Loeb (Univ. 
of Penna. JMed. Bull, July, 1905) have both recorded the occurrence 
of sarcoma succeeding the original carcinomatous tumors after 
some generations of transmissions. This would not necessarily 
suggest the direct transformation of the cancer into sarcoma, as 
much as that in the course of growth the proliferating epithelium 
had induced such changes in the connective tissue portions of 
the tumor as to cause them to acquire an analogous energy of 
atypical proliferation, and that perhaps this latter tissue or, what 
perhaps is more * probable, immune bodies, reactively de- 
veloping to the cancer, have caused the disappearance of the epi- 
thelium itself. The known spontaneous disappearance of cancers 
(cf. Gaylord and Clowes : Surgery, Gynecology and Obstetrics, 
June, 1906) speaks in favor of the existence of such cytolytic factors. 
Gaylord's success in obtaining a serum from mice spontaneously 
recovering from cancers, which on injection into mice having in 
their bodies actively growing tumors of the same strain cawses 
them to recover, speaks in the same line ; and the fact that an ex- 
tract of a tumor (v. p. 339) injected into the body of the original 
animal having other nodes of the same growth in its body, strongly 
supports the same idea. Tentatively then it may be held that in case 
of cancers at least the present tendency is not so much to accept the 
existence of a specific parasitic cause for the growth as to believe 
that once established as an independent focus of growth by some 
such method as is suggested in Ribbert's isolation theory, the epi- 
thelial cells become themselves, as it were, practically parasitic in 
the organism of which they were once an integral part ; that they 
grow as parasites and act as parasites ; and that the body reacts to 
their presence as it does to other parasitic organisms, and endeav- 
ors (sometimes successfully) to produce cytolytic or other protec- 
tive reactions which will tend to destroy the cancer cells. This 
view opens an attractive and wide field for application in many lines, 
not merely therapeutic, and suggests reasons which may explain 
the special prevalence or special failure of secondary growths in 
different systems and organs of the body, as it may be supposed 
that all parts are more or less open by the lymph or blood streams 
to the reception of secondary tumor emboli.] 

All other contributions dealing with cancer parasites (cancer 
bacilli, blastomycetes, etc.) recognized by microscopic methods have 
originated from mistaken interpretations of the microscopic pic- 
tures presented in various examples. 



400 



Tumors. 



The dissemination of the cancer into the tissues, as above indi- 
cated, occurs primarily from the penetration of the multiplying epi- 
thelium into the lymph spaces. They here form tubular or solid 
laminated cords, push aside the endothelium and other connective 
tissue elements, and by continuous progression of growth force their 
way deeper into the tissues, between the muscle fibres and beyond. 
In this way, for example, a growth on the surface of a mucous 



^^ 




Fig. 118. 
Lung of dog with metastatic cancer nodes (thyroid cancer). 

membrane forces its way through the muscularis mucosa and onward 
into the muscular tunics and serous coat of the tube. In the lymph 
passages, by continuity of growth the cords of cancer cells, may 
extend as far as the nearest lymph glands ; or individual cells loos- 
ened in some way may be carried by the lymph current to the latter 
and to more distant portions of the lymphatic system. Multiplica- 
tion of the tumor cells in the tissue of the lymph nodes, and the re- 
active inflammatory proliferation of the connective tissue of these 



Cancer. 401 

structures, lead to marked chronic enlargement of the glands 
(lymphogenous cancer metastases) , one of the clinical character- 
istics of the cancerous affection. Passing from the lymph glands 
the cells of the growth may by following the course of the efferent 
lymph vessels, pass into the blood (anterior vena cava) ; or they 
may gain entrance to the blood by direct penetration of the blood 
vessel wall in their growth. In either event the cells are carried 
onward with the blood stream and form new foci wherever they 
may lodge in the capillaries and give rise to the formation of nodes 
(hematogenous, embolic cancer metastases) . 

Metastatic nodes are as a rule round, and multiple or dissemi- 
nated because the cells have been widely scattered through an ex- 
tensive area of vascular distribution. As a rule they are first sit- 
uated in the lungs, because the cells are very likely to penetrate 
into a vein and be carried through the right heart and into the 
lungs ; in case of primary cancer of the stomach, intestine or pan- 
creas the liver is apt to be involved, by convection through the por- 
tal vein. Should isolated cells pass through the pulmonary capil- 
laries and get into the general circulation by way of the left heart, 
other portions of the body, as the spleen, kidneys or bones, may be 
involved by dissemination of the metastatic cells. Sometimes, too, 
when these cells penetrate into bloodvessels they grow into cord- 
like processes along the vascular lumen; solid plugs of cancer cells 
as thick as lead pencils may occasionally be found extending in 
the thyroid veins from a cancer of the thyroid gland, even down 
into the thoracic cavity. The vascular lumen becomes more or less 
obstructed and the secondary thrombi formed are very likely to lie 
invaded by the cancer cells. 

As the tumor enlarges it compresses and pushes aside all the 
elements of the organ with which it comes in contact; in their pene- 
tration into the deeper tissues and by their lateral extensions the 
cellular roots of the cancer distend and occupy the lymph spaces. 
pushing aside whatever gland-tissue, muscle or nerve may be 
present, spreading out beneath the epithelial covering of mucous 
membranes or integument and perforating layers of epithelium which 
they may encounter. Pressure atrophy and necrosis o\ the surround- 
ing tissue and tissue-destruction from the accompanying inflamma 
tion result from the cancerous infiltration, even hard bone and 
cartilage, perhaps, being broken down In these changes. As the tu- 
mor tissue multiplies beneath the epithelial layer of a surface it raises 
it Up, spreads out in larger and larger area close to the surface 



402 



Tumors. 



and develops in nodular prominences. By cropping out on the 
surface, by perforation at one or more places of such a protuber- 
ance, it may become a direct surface growth with nodulated, uneven, 
undulating elevations and more or less fissured surface. The in- 
flammatory infiltration of the stroma, exaggerated by the entrance 
of extraneous irritants into the exposed growth (contact with air, 
intestinal contents, dirt or bacteria), is likely in such event to bring 
about an ulcerative, foully suppurating destruction of the surface 
of the cancer (cancerous ulcer). In case of penetration into asep- 
tic cavities, especially the peritoneal (gastric cancer, cancer of the 




Fig. 119. 
Cancer of tail of cow. 

intestine, cancer of kidney), transplantation of epithelial cells loos- 
ened from the growth may be brought about by the intestinal peris- 
talsis (by movements of the lungs, diaphragm and heart in the 
chest) and give rise to extensive secondary carcinomatosis in the 
serous membranes by their growth. The secondary formations are 
at first small grayish-white nodules {miliary carcinomatosis), but 
later, by confluence of the enlarging cancerous foci and the accom- 
panying inflammatory changes, a diffuse cancerous peritonitis or 
pleuritis may be established. 

The morphology of the epithelial cells of which a cancer is com- 
posed corresponds in a general way with that of the epithelium 



Cancer. 



403 



from which the tumor took its origin ; in a greater or less measure 
the cancer cells preserve the peculiarities of the epithelium of the 
place of inception, as a tendency to keratinization, to formation of 
mucin and other secretory substances. This retention of original 
characteristics, which is well seen in the metastatic nodes, often 
makes it possible to determine from microscopic examination the 
primary source or origin of a cancer. This is, however, often sub- 
ject to modification. The growth of epithelial cells in unfamiliar 
positions, their separation from their normal substructures, must 
directly, because of the altered nutritional conditions and the vari- 
ous factors of tissue resistance, occasion variation in their 
shape and size. In consequence we often meet with morphological 
variations and anomalies which differ so widely from the original 




Fig. 120. 
Cancer of glans penis of horse. 



characteristics of "the mother cells, that it may be quite impossible 
to come to any conclusion as to the source and type of the tumor 
from the morphology of its individual cells. In addition to this 
polymorphism of the cancer cells there may also occur one or other 
of a variety of retrograde metamorphoses in the luxuriantly grow- 
ing and irregularly nourished cells, rendering them completely un- 
recognizable ; so that at times the real character of the cellular ele- 
ments can be made out only in the more recent parts of the tumor. 

Corresponding to the major types of cutaneous, mucous mem- 
brane and glandular epithelium, three classes of cancers may with 
Durk be recognized : 

1 — Surface cell cancers of the skin and mucous membranes cov- 
ered with /Jul epithelium (called briefly by most authors squamous 
epithcliomata.) 



404 



Tumors. 



2 — Surface cell cancers of mucous membranes covered with cyl- 
indrical epithelium (cylindrical cell cancers). 

3 — Glandular cell cancers [carcinomata]. 

Squamous cpithcliomata, originating from the skin and mucous 
membranes covered with squamous epithelium, manifest their epi- 
thelial proliferation by forming solid cords of cells penetrating the 
deeper tissues, these cords for the most part made up of cells of the 
type found in the stratum Malpighii. The prickle and ridged borders 
of the cells, the protoplasmic processes extending through the in- 




Fig. 121. 

Secondary carcinomatosis of serous surface of liver and omentum, of horse ; 
primary growth of cancer in the ovary. 

tercellular cement (so-called intercellular bridges) are usually well 
marked, and the cells are arranged in layers as over the papillary 
layer of the cutis ; and in consequence we usually find the cells next 
to the stroma of the tumor of a cylindrical form, the next layers 
cubical, and the inner parts of the cord occupied by squamous cells. 
The epithelium in its growth has no opportunity for desquamation 
in these connective tissue spaces, and the old and first formed layers 
must necessarily be found in the central part of the plug-like cord ; 
being derivatives of epithelium subject normally to keratous 
change, the cells of a squamous epithelioma usually also undergo 



Cancer 



405 



keratinization, and here, too, the change affects the older cellular 
elements. The interior of the cancer roots show these flat cells, 
homogeneous and staining diffusely with eosin or fuchsine, with 
their nuclei poorly shown or entirely lost, precisely as those of the 
surface of the epiderm. In consequence on cross section an onion- 
like concentric lamination of the cells is apparent, with the cells 
bent in crescentic manner and applied upon each other like flat 




Fig. 122. 

Microscopic section of a squamous epithelioma of urinary bladder of cow (low 
power). Epithelial cords have grown in between the smooth muscle fibres. 

scales. These horny plugs can sometimes be picked out entire with 
the knife and are called cancer pearls | "pearly bodies," "squamous 
cell or concentric nests"]. The arrangement of layers otherwise 
is apt to be quite irregular, the composite network of epithelial 
roots forming at places broad, thick masses with wavy outline, at 
others delicate, line-like threads. 

The stroma of the squamous cell cancer, present in varying pro- 
portions in different cases, is usually the seat of a marked round 



406 



Tumors. 



cell infiltration, a true inflammatory infiltration ; and the wandering 
cells may be found penetrating even into the epithelial plugs. 

In cylindrical cell cancers the cylindrical epithelium, extending 
in its proliferation into the deeper tissues, laterally and, together 
with its connective tissue, also superficially, usually forms gland- 
like tubes which branch out in different directions as narrow or 
wide hollow offshoots. The proliferating columnar cells may re- 




Fig. 123. 
Microscopic section of a squamous epithelioma of glans penis of horse. 

main in a single layer or become stratified, in the latter case under- 
going various changes in shape corresponding with the prevailing 
pressure conditions, goblet cells peculiar to the mucous membrane 
often being met in great numbers. 

Glandular cell cancers, as far as the morphology of their cells 
is concerned, are as varied as the types of cells in the different 
glands of the body. As in adenomata, in these growths the specific 
gland tissue repeats itself in tumor form. The retention of the 



Cancer. 



407 



tubular arrangement of the cells, and the simple (one layer) lining 
of these tubes may so well preserve the gland pattern that the name 
adeno-carcinoma has been applied to these and to the tubule-forming 
cylindrical cell cancers. The resemblance to the original gland may 
be so great that not merely the morphology of the most of the tumor 
cells remains unchanged, but even the production of secretory sub- 
stances in the tumor tissue is distinctly analogous. Thus hepatic 
cancers have epithelial cells of precisely the same type as the polygo- 













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Fig. 124. 
Microscopic section of adenocarcinoma of kidney of horse. 



nal hepatic cells, arranged in anastomosing trabecular columns, with 
capillaries and scanty connective tissue extending between them; 
and these epithelial cells secrete bile, the tumor sometimes being 
stained an intense yellow or green color from the latter. Thyroid 
cancers, made up of low, cubical, thyroid epithelial cells and a vas- 
cular stroma, show as a rule a practical duplication of the structure 
of the thyroid gland in the production of colloid material and in 
the alveolar distension of their epithelial offshoots. Cancers of the 
intestinal glands repeat the tubular invaginations of the Lieber- 



408 



Tumors. 



kiihn's crypts with of course considerable enlargement of the lumina, 
and are characterized by marked production of mucin and by the 
presence of numerous goblet cells among the lining epithelium. 
Mammary cancers have so marked a tendency to fat formation from 
their cells arranged in alveoli, that milk-like fluid is usually found 
filling the tubular cancerous spaces ; and ovarian cancers undergo 
the + formation of cysts which might well be mistaken for the 
follicles 




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Fig. 125. 

Hard adenocarcinoma of mammary gland of a bitch; shows the predominance of 
the connective tissue stroma, the preservation of duct and acinous arrange- 
ment of epithelium (as at a), but also the irregular and excessive epithelial 
formation of solid cords and infiltration of tissues by their penetrating 
anastomoses (as at b). 



The same structure, too, is repeated in the metastatic nodes in 
the lungs, peritoneum and elsewhere, proving their derivation from 
the primary tumor and its original source. 

This correspondence in cellular character between the carcinoma 
and the gland from which it originated is, however, not always ap- 
parent, the atypical nature of the growth manifesting itself in the 
extension of the cells beyond their normal limiting membranes, 



Cancer. 409 

their dissemination in the surrounding tissue and their metastasis, 
and in the fact that the epithelial outgrowths do not form com- 
pletely hollow passages, but are seen in massive proliferation as 
solid cellular roots. The ducts of the involved structure are filled 
with epithelium, and the cells show a great variety of altered shapes 
depending upon the pressure conditions prevailing, fusiform, 
rounded, irregular, etc. The connective stroma varies much in its 
degree of development, and is sometimes found in villous masses, in 
folds and laminated processes just as in adenomata, especially when 
there are spaces and larg'e cavities in the tumor (cyst carcinoma 
papillar e). 

[The essence of the histological fault of any cancer lies in the 
fact that in its proliferation the epithelium of the tumor does not 
maintain its normal topographical relations, but grows through its 
limiting membrane and is found infiltrating to a greater or less 
degree the tissue about it, either as isolated cells or as roots or cord- 
like groups of cells. In most cases, too, increase in the amount of 
epithelium is recognizable not only by this infiltrative or metastatic 
excess but by an excessive number of cells upon the surface in- 
volved, or within the tubular space? or the alveoli of the affected 
portion of the gland ; thus instead of a single layer of cells fining the 
tubular canals of a cancerous area of endometrium, it is common 
to find a number of layers and the tubules distended and branched 
as the author above indicates. This excess, however, is by no means 
an essential feature, many scirrhous carcinomata showing a mani- 
fest reduction in the epithelial elements below that realized as nor- 
mal to the original gland and to the ordinary cancers of the 
same organ ; and in such cases one finds not only relatively few 
epithelial areas but also no excess of layers in the tubular lumina, 
the cells which do line such spaces being in fact themselves small, 
atrophic or degenerative. It will be found, however, that many of 
the cells in these have no relations to tubes or alveoli and are clearly 
free in the lymph spaces of the connective tissue stroma; and care- 
ful examination of the gland-like spaces or tubes will somewhere 
show the direct growth of the epithelium into the surrounding 
tissue beyond the proper membrane. The 'existence of karyokinetic 
nuclear figures is of some value as indicating the active prolif- 
erating state of the epithelium. 

The editor believes that for practical purposes in microscopic 
diagnosis of cancers of the author's two varieties, cylindrical cell 
and glandular cell cancer, it is appropriate to recognize two types 
according to the existence or non-existence of marked resemblance 



410 Tumors. 

to glands. Those cancers which exhibit a distinct tubular or acinous 
structure i from which, however, the deviations just indicated are 
evident ) are adenocarcinomata. All of the types of cancer here 
under discussion may be said, at least in their early period, to be 
adenocarcinomata. Those in which the proliferative and infiltra- 
tive processes have so advanced as to destroy the original gland 
resemblance, so that definite tubes or acini are not well or numer- 
ously recognizable, may well be called carcinoma simplex. These 
merely represent more advanced stages of the first, and are more 
common as actively growing and extending cancers. 

The stroma of true cancer, as the author remarks, is exceedingly 
variable and is often the basis for special sub-divisions of the 
growths. Thus it may be relatively small in amount, the epithelial 
elements predominating ; this condition underlies the group of soft 
cancers (medullary cancers). Or it may be greatly in excess, 
markedly predominating over die epithelium of the growth, dense 
and fibrous: such growths are the well known hard cancers or 
scirrhous cancers (substantive scirrhus). The connective tissue 
stroma may exceptionally be found largely or totally of a gela- 
tinous tyoe (carcinoma myxomatodcs) ; or highly cellular and evi- 
dently of a sarcomatous type (carcinoma sarcomatodes). Other 
types of connective tissue may also be encountered in varying 
amounts in the more highly mixed cancers.] 

The external shape and other macroscopic characters of cancer 
vary with the location of the original growth, the structural con- 
stituents of the tumor and the age of the neoplasm. Cancers de- 
veloping on the free surfaces of the skin and mucous rnembranes 
[squamous epitJielioinata, surface adenocarcinomata] often appear 
as cancerous ulcers. The infiltrative growth causes a thickening 
of the membrane, with the [ulcerated] exposed surface uneven 
with nodular prominences, suppurating, red or dirty dark brown, 
and perhaps covered with crusts, with the base and wall shown 
in cross sections as a more or less defined growth and as a light 
gray bacony zone often penetrating by root-like extensions into the 
deeper tissue. The normal epiderm is usually sharply denned along 
the border of the ulcerating exposed tumor surface. In mucous 
membranes, as the urinary bladder, cancer often forms merely super- 
ficial, undulating, slightly elevated thickenings [flat tabular swell- 
ings] , recognizable from simple inflammatory changes by the 
accompanying enlargement of the lymph glands, the infiltration of 
the growth into the muscular lavers and bv the definition of the 



Cancer. 



411 



grayish-white medullary tumor tissue seen in cross sec- 
tion. Of course the microscope affords the conclusive diagnosis. 
These surface cancers may also develop into cauliflower forms 




Fig. 126. 
Cancer of gum (squamous epithelioma) of horse. 



(carviol), masses of a light gray to more reddish hue, growing 
from the surface of the skin or inneons membrane, the surface sub- 
divided and overlaid by a suppurating, ichorous, pulpy mass ot dis- 
integrating cancer tissue. 



412 Tumors. 

In the interior organs cancers form nodes of widely varying, 
dimensions, sometimes sharply circumscribed and rounded, or with 
their tissue gradually merging by infiltrative extension with that 
of the synchronously enlarging organ. The whole organ, as a 
kidney, may be incorporated into the tumor tissue, and in its stead a 
shapeless mass of cancer is met weighing perhaps from one to 
fifteen kilograms. The tendency to perforate to the surface of the 
involved organ is a marked characteristic of cancers. Another 
peculiar feature is the production of cancer umbilication, seen 
rather irregularly in the smaller nodes [secondary nodes] about 
to perforate through serous surfaces ; it is a central depression 
seen in these nodes due to the prominence of the marginal 
growth and destruction of the interior of the node. On section 
of cancers a milky fluid or juice, briefly known as "cancer milk," 
may frequently be obtained by scraping the cut surface or may be 
expressed in drops by compression with the fingers ; upon micro- 
scopic examination it is apparently almost entirely composed of the 
epithelial cells (with fatty degenerative changes) of which the 
cancer is constructed. 

The secretion of mucus and of colloid substance, as seen in 
adenocarcinomata of mucous membranes and follicular glands 
(ovary, thyroid) and the retention of these materials in the tumor 
tissue sometimes gives an unusual softness and transparency to the 
cancerous growth, the name gelatinous cancer being often used in 
connection with such examples. [The term colloid cancer has, from 
confusion, been employed indiscriminately in these cases. Colloid 
cancer, using the term in its strict sense, is practically confined to 
the thyroid gland, and even there much of the gelatinous material 
contained in it is not definitely colloid, but rather mucoid. The 
use of the term colloid for these gelatinous cancers in other situa- 
tions of the body (stomach, intestine, ovary, etc.) is almost sure 
to be wrong; the change really being a collection of some type 
of mucin within the epithelial cells and perhaps also in the tissue. 
The cells which in older text books are described as "colloid seal- 
ring cells" are really nothing but mucoid goblet cells, quite like those 
found in a catarrhal mucous surface, but modified by pressure so as 
to have a rounded shape, the mucin in their interior pressing the 
nucleus and a part of the cytoplasm to one side so as to form the 
prominence compared to the seal of a ring.] On the other 
hand some cancers come to be very dense and cicatricial in consist- 
ence in case the associated growth of their connective tissue should 
be unusually marked in quantity, in density of fibrillation and in- 



Cancer. 413 

durative. The epithelial elements in such examples may become 
very unimportant structural factors ; these hard specimens are 
known by the names scirrhus, scirrhous cancer. 

According to statistics compiled by Casper, Frohner and Sticker, 
cancers [among animals] are most frequent among dogs (three 
per cent.) ; horses rank next in order, and after them cats. 
Just as in man cancer in animals is a disease developing principally 
in middle and later life. This is probably the reason for the in- 
frequence of these tumors in cattle, sheep, goats and swine, such 
animals not attaining an advanced "age because of their use for meat 
supply. The skin and its junctions with the mucous membranes 
are the most frequent seat of growth [for squamous epitheliomata] , 
anal cancer in the dog and cancer of the glans penis, gums 
and lips in the horse being frequently met with. The mammary 
glands and thyroid gland of the dog are comparatively frequent 
points of primary involvement [adenocarcinoma or carcinoma sim- « 
plex according to the degree of atypical structure to which the 
growth is advanced] . 

In human beings cancer of the stomach and of the female uro- 
genital organs constitute a high proportion of these growths ; in 
animals these organs are affected by cancer to a far less degree.* 
As far as the rest of the body is concerned it may be said that pri- 
mary cancer has been observed in all the epithelial organs. In 
structures which do not possess epithelial cells (lymphglands, mar- 
row, spleen, muscles, etc.) cancer can occur only in metastases (in 
rare exceptions also from embryonal germinal misplacements). 
Such metastatic growths sometimes become of greater bulk than 
the primary tumor, especially those of lymph glands. f 

The general peculiarities of cancerous growths, their irrepressi- 
ble penetration into the tissues in every direction, the difficulty of 
thorough operative removal of all their roots which is only occa- 
sionally successful in the early stages of the cancer and if incom- 
pletely accomplished invariably results in recurrence, the destruc- 
tion of the affected organ and the certainty of metastasis, stamp these 
tumors as highly malignant autoblastomata. In the course of the 
cancerous affection, the severity of which is determined by the rap- 
idity of dissemination and the location of the growth and the impor- 
tance of the tissue involved, there usually develops a condition o{ 

* For details see especially (lie statistics of Sticker, Arcliir. f. Klinisch. Ohir 
tirgie, Bd. 65, Berlin, 1002. 

t If the primary growth lias been removed by operation and (his fact be 

unknown to the examiner, or it' the scar a1 the affected place be overlooked, the 
secondary formations may give the erroneous Impression of being primary tumors 



414 Tumors. 

general emaciation, anaemia and bodily weakness, known as can- 
cerous cachexia, due at least in part to the reaction upon the 
system by toxic products formed in the cancerous tissue. 

[The cachexia of cancer is of course induced the more early and 
markedly in case the cancer involve some of the organs of nutri- 
tional importance to the animal, as the alimentary tube or pancreas ; 
the faults of nutrition being important contributors to the produc- 
tion of oligaemia and loss of flesh and strength. The idea of toxic 
factors, although usually not urged by writers because of our ig- 
norance, is, however, probably an important one, these toxines aris- 
ing from the secretory activity of the tumor tissue or as products 
of tissue metabolism or destruction. The metastatic tendency, in- 
volving the progressive affection of more and more of the body by 
cancerous foci, must of course be an important factor of malig- 
nance. The occurrence of metastases varies greatly with the type 
* of the tumor and with the definite resistive power which the body 
exerts against these practically parasitic cells, this resistance being 
apparently not at all uniformly possessed by the various organic 
systems or by different individuals. In a general way it may be 
said that the squamous epitheliomata are likely to disseminate more 
slowly than the other varieties, progressing more regularly by a con- 
tinuous invasion of the lymph spaces and channels, and therefore 
showing a greater tendency to local and neighboring infiltration and 
node production. Distant metastases are to be met with but are not 
as frequent as in the cylindrical cell and glandular cell cancers. Of 
the latter groups in a rough way, to which exceptions are common, 
it may be said that those that manifest in their structure the great- 
est departure from the tubular and acinous types (carcinoma sim- 
plex) are those showing the more rapid and extensive metastatic 
tendency ; the adenocarcinomatous forms the less. Both are, how- 
ever, more apt to give distant metastasis than the squamous cell 
form. The condition of the stroma makes a difference as well, the 
soft medullary types with a small amount of stroma being more 
metastatic and the hard scirrhous varieties tending to ■ remain local 
for a longer period. It is said that cancers as a group are char- 
acteristically generalized by way of the lymphatic system, in contrast 
to sarcomata which are more frequently conveyed by the blood cur- 
rent. This is, in the main, true, and the usual rule is to find the 
lymph glands into which the lymph drainage of the cancerous part 
passes the seat of secondary cancers. Yet it is by no means neces- 
sary. The route of metastasis and in a great measure the tendency 



Epithelial Cysts. 415 

to give rise to metastasis are explicable on mechanical grounds. 
The cells of squamous epitheliomata are usually large cells and are 
less easily displaced from their site of formation than many of the 
smaller cells of the cylindrical cell and glandular types of cancers ; 
and as a group all epithelial cells are larger and less easily dis- 
placed than the small round cells of small round cell sarcoma. These 
last mentioned growths have cells comparable to the small lympho- 
cytes which are always and readily passing with the blood through- 
out its entire capillary system. It amounts therefore to the general 
rule that, whatever tumor cells may be able to gain entrance to some 
small capillary blood vessels in the tissue in which they are growing, 
the sarcoma cells have a better chance of convection than do the 
epithelial cells. On the other hand sarcomas in their growth, direct- 
ly from and in the connective tissue structures in which the blood- 
vessels are distributed, are more favorably situated as early tumors 
to gain access to these vessels than are the epithelial cells, which 
primarily are separated from the blood stream not alone by the ves- 
sel walls but by more or less connective tissue and by remnants, at 
least, of a membrana propria. In their mode of growth cancers 
primarily are more likely to gain entrance to the lymph spaces ani 
channels, and are therefore from the first more favorably situated 
to follow this system provided the spaces and channels are of suf- 
ficient calibre to allow the convection of the epithelial cells (as they 
usually are, in comparison with the minute blood capillaries). Yet 
granting such factors as these, as determining the usual course and 
occurrence of metastasis, exceptions must arise and are constant 1 }- 
being seen. If a sarcoma grow in lymphatic tissue (a lymphosar- 
coma for example) it is very likely, whatever the size of its cells, 
to follow the lymph current to the neighboring nodes; and if in 
some situation (as in stomach or intestinal wall where the larger 
radicles of the portal vein are close to the cancerous growth start- 
ing in the mucosa) the cancer cells be afforded easy access to 
bloodvessels of sufficient calibre to accommodate their size they will 
be found to give rise to hematogenous metastasis (as the portal 

convection of gastric cancer to the liver).] 

* 

Epithelial Cysts, Dermoid Cysts, Odontomata, Mixed Teratomata. 

There are a number of tumor-like formations which, as hollow 
epithelial lined sacs, limited to their place of development, originate 
from embryonic cellular misplacements. These are cysts I »; ioJotu, 
vesicle) which are not produced from mature glandular Organs 



41 6 Tumors. 

from simple retention of their contents and dilatation of their 
canals and are not formed in the loose structures of the body from 
exudation into them or from liquefaction of the tissues themselves, 
but take their inception in early embryonic life from displaced and 
isolated portions of organs, organic rests and hollow offshoots of 
such structures, and acquire an independence of growth. 

The simplest type of these cysts is the epidermoid cystoma or 
epithelioma cystica m, a sac of the size of a nut, a hen's egg or even 
of a fist, which is completely filled with loosened squamous epider- 
mal cells almost all in a keratous condition ; sometimes cholesterin 
is found mixed in with these. Bonnet met a genuine example of this 
type in the .cranial cavity of a horse. All these cysts containing 
squamous epithelium doubtless originate from ectodermal cellular 
inclusions in foetal life, conceivable as occurring from friction of the 
skin by amniotic strands. Their occurrence in the cranial vault, near 
the aural and temporal region, suggests that displaced portions of 
the epithelium of the branchial arches constituted their original sub- 
stance, and in case of those developing in the brain, from the med- 
ullary folds, the ectoderm must certainly play a part in their 
origin. Experimental studies by Schweninger, E. Kaufmann and 
Ribbert show that epithelial cysts can be readily produced artifi- 
cially by insertion of a bit of epiderm, conjunctiva or tracheal mu- 
cous membrane into the peritoneum or under the skin. When the 
epithelial cells are supported by a little connective tissue to preserve 
their nutrition they grow over the interior surfaces of the wound 
with which they have been placed in contact, and form the lining of 
the hollow space, the latter being occupied by the wound secretions 
and desquamated epithelium. Epithelial lined cysts may also be 
produced, as pointed out by these authors, by suturing over a cir- 
cumscribed bit of epiderm the adjacent loosened borders of skin; 
the bit of epiderm beneath the sutured parts grows and fills in the 
space beneath the elevated cutis (Ribbert). In man as the result of 
accidental misplacement of epithelium in operations, or of cutaneous 
lacerations, similar cyst formations are well known to occur. Such 
results are known as traumatic epithelial cysts. 

As derivatives of the skin in its entirety, of the cutis with its 
glands, of hairs and epiderm, may be mentioned the dermoid cysts 
or hair follicle tumors ( dermatocystis congenita or cystoma der- 
moid 'es) , which occur comparatively frequently in cattle and horses, 
situated in the subcutaneous connective tissue. They appear from 
the exterior as flat cutaneous swellings or may be found acci- 
dentally in skinning or eating beef. The cyst varies from the size 



Dermoid Cysts. 417 

of a nut to that of a fist, is rounded and filled with a bunch of 
tangled hair and a dirty brown fluid consisting of secretion from 
the sweat-glands, fat and desquamated epithelial cells. The wall 
of the sac, which may be easily shelled out of its bed, is thin, quite 
like the fibrous structure of the cutis, and lined on the inside 
with epiderm and attached hairs, loosened hairs occurring in the 
contents as free bunches. Microscopically the wall has all the 
appearances of the cutaneous structure. These dermoid cysts are 
met particularly in the region of the neck and jaw, generally 
developing in these situations from tissue derived from the 
branchial arches (branchiogenous cysts) ; they are also met about 
the shoulder or elbows, in which cases they may be referred to 
faults in the development of the anterior limb bud (Leisering. 
Johne, Grams and others), in the umbilical region, and in the 
testicles and ovaries. 

As early as 1854 Remak explained the origin of dermoid cysts 
by conceiving an abnormal development of the arches and resultant 
enclosure of a bit of the germinal epidermal layer as their basis ; 
and it may also be possible that injuries caused to the skin in the 
region of fissures may give rise to them, provided the borders of 
the fissures become the seat of a cicatrizing proliferation and, 
further, provided the base of the skin fissure becomes isolated and 
brought to lie underneath the scar. 

The dermoid cysts of birds contain feathers (feather-follicle 
cysts, cystoma penniferum) and are found from the size of an egg 
to that of a fist within the abdominal cavity of geese, more rarely in 
ducks and chickens. The cyst, surrounded by a thick layer of fat, 
is sometimes free in the peritoneum or may be attached by a peri- 
toneal fold to the ovary and lumbar region. The number of feath- 
ers (the plume not unfolded because wet with fluid) may reach 
several hundred. 

Analogous to the dermoid cyst but not growing in cystic form, and 
appearing as protruding islands of hairy skin, arc the dermoid teratomata 
of the cornea (also of 'palpebra tertia), which arc met comparatively com 
monly in cattle and dogs. They arc congenital anomalies .and originate 
from a misplacement or transplantation in the formation o\ the palpebra] 
fissure. 

In the same way as from the epiderm and cutis cystic foci may 
arise from separation or misplacement of their cells, epithelial 
lined cysts may also develop from the mucous membrane 
tubules and glandular ducts in embryonic life from budding or 
other anomalies of development, particularly from "rests" oi 



4i8 



Tumors. 



gland tissue {adenocystoma). These entodermal cysts are lined 
by columnar epithelium, sometimes ciliated, and in man are found 
in the liver, intestine or peritoneum, in the neighborhood of the 
trachea and bronchi, and in the neck, varying in size from that 
of a pin-head to that of an adult human head. In animals they 
most usually arise from rests of the original urinary structures, 




Fig. 127. 
Cystic kidney of hog (section). 

the Miillerian or Wolffian ducts, and are found as transparent 
vesicles of the size of a millet seed or pea or sometimes larger, 
along the broad ligaments of the uterus, in the fimbriae of the 
oviduct, and in the epididymis. The congenital cysts of the 
ovary, occurring as single or multilocular and closely packed 
cysts of this organ, and containing a thin mucoid and sometimes 
bloody material, are further examples of the same type. Con- 
genital cysts of the kidney are also regarded as results of devel- 
opmental disturbances, converting the kidneys, usually bilater- 
ally, into a grape-like mass of vesicles with watery contents, 
between which an inconspicuous amount of parenchyma is found 
reduced mainly to thin connective tissue septa (cystic kidneys, 
vesiculated kidneys). This anomaly is supposed to be due to a 
failure of union between the uriniferous tubules and the develop- 
ing glomeruli, these two parts growing separately (Ribbert). 
The term odontoma and odontoblastoma are applied to mon- 



Odontoma. 



419 



strous tooth-formations, which arise from faults in the embry- 
onic development of dental substances and present themselves 
either as excrescences on the teeth, of bone-like hardness and 
composed of cement and dentine, or as abnormities in which an 
entire tooth has been changed into a shapeless, nodular form 
with enlargement ; or in which in combination with an accom- 
panying proliferation of the soft connective tissues a compound 
dental tumor has been produced. These neoplasms are always 
congenital, either becoming apparent at the time of the eruption of 
the tooth or the teeth fail to erupt and a tumor slowly develops 
in the alveolar portion of the jaw beneath the gum, bulging the 
latter and expanding the bone as it enlarges within the alveolus. 
The composition and form of these odon- 
toblastomata vary considerably with the 
part taken by the different tissues con- 
cerned in embryonic tooth formation, the 
dentine and its covering of enamel, the den- 
tal sac and the peripheral alveolar bone. 
The simple odontoma durum, now and 
then seen on single teeth in the cow and 
horse, occurs as a mass about the size of 
a nut, rounded, hard as bone, and usually 
surrounding the crown or more rarely the 
root of the tooth. In other instances, as 
observed by Wedl and Magitot, the whole 
tooth lying within the alveolar process is 
changed into a mass of bony hardness as 
large as an orange or possibly weigh- 
ing as much as a kilogram. The name 

odontoma mixtum is applied to a growth composed partly of 
fibrous tissue, bloodvessels; odontoblasts and agglomerated tooth 
papillae, with the hard parts in rudimentary unshaped masses of 
dentine and enamel over the surface or mixed in the interior. 
Sutton has met with a mixed growth of this type weighing seven 
hundred grams in a horse. Similar tumors, sometimes only 
enclosing in their structure a single hard rudiment of a tooth, or 
sometimes containing a number, possibly several dozen, mis- 
shapen or fairly well formed teeth, occur as cysts or bunches 
of cysts, completely included by fibrogelatinous dental sacs and 
alveolar bone capsules (odontocystorna capsulare, cystoma denti- 
fernm alveolare). In other instances the proliferation of the 
bony capsule is especially marked, surrounding the dental sac- 




Fig. 128. 

Odontoma of incisor tooth 
of cow (natural size). 



420 



Tumors. 



cular tumor and the deformed tooth, and giving' rise to the tvpe 
known as osteocystoma capsular e dentiferum. Occasionally in 
young horses at the base of the ear over the temporal bone cysts 
may be found which contain one or several imperfect teeth, 
usually opening by a fistulous sinus upon the skin ; these are 
blind tubular invaginations from the skin, lined with mucous 
membrane and provided with a bony covering or with small 
bone platelets in simulation of the alveolar process of the jaw; 
they originate from the branchial arches and are known as 




Fig. 129. 

Odontocyst of lower jaw of cow. 




Fig. 130. 
Osteocystoma dentiferum of horse. 



branchiogenous dental follicular cysts -(odonto-teratoma bran- 
chiate, odontocystis branchiogenetica)* This type of cysts is 
only rarely met in other animals; Siedamgrotzky encountered 
two dental cysts in the ethmoidal turbinate in a hog; Verwey has 
recorded one in the petrous portion of the temporal bone in 
a dog; Hertwig met a dental cyst in an ox. 

Teeth are sometimes found in dermoid cysts and teratomata 
in other parts of the body, especially in this type of growth in 

* For fuller description v. Kitt, Lehrbuch der pathoh Anatomie der Haustiere, 
Stuttgart, F. Enke's Verl. U Aufl., 1901. 



Dentigerous Cysts. 421 

the ovary and testicle (heterotopic odontoteratomata) . Gurlt 
recorded a testicular tumor of a horse, about the size of a fist, 
of stony hardness, containing six molar teeth (three separate, 
three merged together), together with thin plates of bone repre- 
senting a rudimentary alveolar process, and a fibrous capsule ; 
in a second instance the egg-sized tumor contained, besides a 
single tooth, a lot of hair and a fluid material made up .of a 
mixture of perspiratory and sebaceous material. 

In addition to the above cysts and dentigerous tumors there 
occur, especially in the sexual glands of both sexes, a number 
of other tumors of complex composition, sometimes showing an 
irregular mixture of heterogeneous tissues of all three embryo- 
blastic layers, sometimes a definite tissue arrangement repre- 
senting clearly the structure of a number of organs. Because of 
their close relation to monsters the collective names teratoma or 
embryoma are used in connection with these peculiar formations, 
which undoubtedly originate from embryonal cells or tissues 
which have been segregated and become independent at an early 
developmental period. 

The external tumors of this type, growing in the superficial 
tegumental tissue or in the mouth, are possibly the results of 
partial cleavage from amniotic threads, as it is known that 
indentation of an embryonic tissue can cause its division and 
double development; and even transplantation may be effected 
from injuries caused by amniotic bands. These external tera- 
tomata usually appear as tumor-like, pedunculated formations, 
of lobulated outline, and are composed of hairy skin, rudimen- 
tary jaws with teeth and mucous membrane covering, fat tissue, 
nerves, muscle and glandular structures. (For illustrations and 
details v. E. Sigl, Monatsheft f. pr. Tierheilkunde, Stuttgart, 
1902.) The compound teratomata developing in the interior of 
the body, especially in the ovary and testicle, may sometimes 
originate from germinal segregations from the primitive seg- 
ments of the vertebral column or from the indifferent cells of the 
Wolffian body; or it is possible, as Marchand's theory would 
make plausible, that they may arise from the separate develop- 
ment of one segmentation cell. According to the experimental 
studies of Roux and others each one of the primitive segmenta- 
tion products of the ovum — that is, each segmentation cell — is 
capable of producing an entire embryo ; thus the possibility 
arises that an isolated segmentation cell in course of progressive 
development may form a group of embryonic tissues, which be- 



422 Tumors. 

cause of irregular nutrition succeed in their later growth in 
forming only an amorphous body of all sorts of organic struc- 
tures mixed together. This, it is likely, enclosed within the indi- 
vidual formed from the other segmentation cells, remains without 
further development, as a tumor. [Many of the so-called ovarian 
dermoid cysts met in human beings are properly of this last 
type,*complex teratomata, frequently containing tissues evidently 
from two or all three of the embryoblastic layers. It has been 
suggested in addition to the above explanations for such terato- 
mata in the sexual organs that they may be the result of seg- 
mentation and development of an unfertilized ovum directly 
within the ovary, a parthenogenetic development. This idea has 
no wide acceptance, but it should be recalled that partheno- 
genetic development is well known in many lower forms of life, 
and that Jacques Loeb has succeeded in causing the development 
of unfertilized ova of sea-urchins bv chemical stimulation. It 
should be added moreover that L. Loeb (Archiv. f. mikrosk. 
Anat. u. Entwicklungsgeschicht. Bd. 65, 1905) has demonstrated 
karyokinetic changes and segmentation of the ovum in the ovary 
of the unfertilized guinea-pig. The theoretical possibility of this 
mode of origin of ovarian teratomata should therefore be accepted ; 
although evidence of its actual prevalence is not clear.] , 



FUNCTIONAL ABNORMALITIES 

Nervous Disturbances — Disturbances of Motion. 

The nervous system regulates the functions of the organs and 
is the intermediary between the corporeal and psychical func- 
tions of the polycellular animal organism. The nervous matter 
may be excited by both external and internal agencies (stimuli), 
and being thus stimulated gives to the tissues the impulse for 
the manifestation of the powers peculiar to them. Alterations 
in the excitability of the nervous system and abnormal stimuli 
which occasion such variations, may result in functional dis- 
turbances of the nervous apparatus and the organs dependent 
upon it. Where the whole central system is altered, these dis- 
turbances are general and may manifest themselves in the widest 
possible range (general nervous symptoms) of abnormal nerv- 
ous phenomena (sensory, motor, secretory, reflex). Where 
definite localities in* the central nervous system are subjected 
to injury, we speak of central local involvement and focal symp- 
toms. In this connection, too, nuclear involvement where the 
nucleus is affected, is differentiated from supra-nuclear in- 
volvement, where the course of the conduction within the 
central system — that is, above the level of the nucleus — is 
the part disturbed; and according as the focus affected lies 
within the brain, in the medulla oblongata or in the spinal cord 
the lesion is said to be cerebral, bulbar or spinal. Where a 
nerve is injured in its course beyond its point of exit from the 
brain or spinal cord to its area of distribution or within the 
latter, peripheral affections ensue. 

General Nervous Disturbances. — The brain and medulla to- 
gether constitute the central organ presiding over the whole 
category of functional activities, and therefore everything which 
causes depression or excitation of cerebral activity must of nec- 
essity bring about a great variety and general distribution of 
disturbances. Every lesion of the deeper centres of the medulla 



424 Nervous Disturbances. 

oblongata, in which the circulatory and respiratory regulative 
apparatus are located, must necessarily inhibit or depress these 
most vitally important functions and thus threaten life. Lesions 
of the cerebral cortex bring about varying grades of disturbance 
of consciousness, which, including all phases of mentality, may be 
collective!} spoken of as psychical disturbances. 

The most severe of the psychic paralyses is cerebrospinal 
concussion (commotio cerebri et medulla). After more, or less 
severe concussion of the head or the whole body by a fall, blow 
or kick, the functions of the brain and cord cease. Anatomically 
there is often nothing to be found in such a case, beyond slight 
hemorrhagic effusions upon the membranes and the skull, and 
gross lesions of the nervous structures are absent. The severe 
symptom complex can only be explained by supposing that 
through the influence of the concussion waves upon the exceed- 
ingly complicated mechanism of the nervous system (compres- 
sion alternating with stretching force) minute structural changes 
must be induced, as destruction of the delicate dendrites of the 
nerve cells (Krehl). 

Cessation of the cerebral function is manifested by complete 
loss of consciousness, loss of all voluntary muscular motility, 
loss of pupillary reactions, weak pulse and coolness of the exter- 
nal surface ; and tends usually, in a few minutes, hours or days 
to death. In other and milder instances onjy a transient loss of 
sensibility occurs. When the cord is the main part involved by the 
concussion there are met paralysis of the extremities, loss of sensa- 
tion in the latter and in the trunk, and disturbances of respiration, 
as the principal symptoms. Sudden and usually brief disturb- 
ance of equilibrium and inability to maintain an upright posture 
(dizziness, zrrtigo), associated with loss of consciousness (faint, 
syncope), occur from disturbance of the blood circulation in the 
cerebral cortex and in the cerebellum ; they may result too from 
trivial grades of general anaemia of the brain, as a decrease in 
the arterial supply, and also occur in passive congestion (cardiac 
disease, compression of jugular veins) or from anatomical 
changes of the cerebellum, aural disease and toxic influences. 
In uncomplicated loss of consciousness the cerebral cortex is 
alone the seat of involvement ; the animal suddenly begins to go 
slowly, stops for a moment, staggers, leans against the shafts 
or other support, turns around in a circle and falls ; then, after 
remaining motionless for a few minutes, attempts with labored 
movements of the limbs to get up, and is gradually able to rise and 



Psychic Disturbances. 423 

resume consciousness. Sometimes vomiting (in dogs) and invol- 
untary discharge of urine and feces ensue. 

(For details see Friedberger-Frohner, Veterinary Pathology, Amer. 
Ed., 1904. W. T. Keener & Co., Chicago.) 

Persistent unconsciousness, coma ( to kQ/jlo., lethargy, from 
Koifidu, to lull to sleep), or sopor (sopor, a sleeping draught), is a 
state of insensibility which is met in serious brain affections, 
intoxications (uraemia) and particularly in connection with 
haemorrhages from the cerebral vessels ; in the last when it 
occurs suddenly and paralysis results, the process is usually called 
a brain or nervous stroke (apoplexia cerebral is, nervosa; 
a-rroTrXrjo-o-eLv, to strike down). When unconsciousness occurs par- 
oxysmally, accompanied by muscular spasms and loss of sensa- 
tion it is known as falling sickness or epilepsy ( y\ i-n-iX-n^is ) ; it de- 
pends upon some functional disturbance of the cortical centres, 
the real cause of which is, however, unknown. Compression of 
the intracranial structures, as from blood clots, tumors, increased 
pressure of the cerebro-spinal fluid, or collections of exudate, 
give rise to the symptoms of compression of the brain (brain 
depression). These consist of general dulling of the senses, a 
somnolent, lethargic attitude, staggering and awkward gait and 
diminution of sensibility. The animal stands as though deaf, 
leans against some adjacent body for support, hangs its head or 
supports it against the wall or manger, and the eyelids are closed 
as if in sleep and the pupils dilated. The animal may be hard to 
move from one spot and may continue for hours at a time in some 
abnormal posture (legs crossed or kneeling), or may run about 
with staggering gait into the wall and all sorts of obstacles, or 
may continually move about in a ring; it is apathetic when 
spoken to, touched, whipped, bitten by flies, etc. ; takes no food, 
or holds its food in the mouth without chewing, pushes its nose 
deep into the water in drinking ; and may show other special 
pressure symptoms according to the particular part of the brain 
affected (reversed movements, riding paces, focal movements, 
dancing or rolling movements, or pressing toward one side). In 
the man and the dog there are also observed peculiar alterations 
of the eye-ground, so-called [choke disc] papillary conges- 
tion (really a papillitis, inflammation of the papilla and optic 
nerve) ; in horses with blind staggers these are not noted 
(merely an anaemia recognized — Friedberger-Frohner). These 
symptoms depend upon the fact that in the first place in the 



426 Nervous Disturbances. 

conditions indicated disturbances of the blood circulation arise, 
as compresison of the large veins before opening into the rigid 
walled sinuses, with resultant stasis, interference with the escape 
of venous blood and cerebro-spinal fluid, and the production of 
increased pressure upon the brain substance ; that, further, in 
the conditions mentioned increased formation of this fluid and 
special tissue changes in the brain may obtain, and perhaps, too, 
toxic influences (bacterial toxines, autotoxines). 

Psychical excitement has its causative factors in hyperaemia 
of the brain, cerebral inflammatory changes, heat or toxic influ- 
ences, and occurs in a number of different degrees of severity. 
The main symptoms are manifested as attacks of insanity 
{mania, delirium furibundum). The animals in these attacks 
suddenly lose their docility, try to free themselves from their 
fastenings, bite their own bodies, make attacks in whatever way 
is natural to them (strike out, kick, try to bite), run into obstacles 
and violently knock them over, stand up on their hind legs and 
throw themselves about with shrill cries, grit their teeth and 
froth at the mouth ; the eyes become staring and wild, the con- 
junctivae injected; and finally the animals collapse and go into 
spasms and convulsions. Especially in dogs of usually affec- 
tionate and lively disposition, well-trained and possessed of 
special intelligence we meet with the widest range of mental 
disturbances, from melancholia to hallucinations (fancied per- 
ceptions), marked confusion and insane outbursts, as in rabies 
(depressed stupid condition, snapping at the air, purposeless 
wandering about, sudden attacks of desire to bite, tearing of the 
animal's own flesh), or in poisoning with deadly night-shade or in 
sunstroke. Similar symptoms of excitement are seen in dogs 
in the autointoxication produced by the portal blood, that is, the 
absorbed products of albuminous decomposition in the intes- 
tine, in Eck's fistula [fistula made between the portal vein and 
vena cava with diversion of the portal blood from the liver]. 
Special nervous excitement and reflex psychic conditions occur 
in some of the diseases of the genital organs (ovarian cysts, 
ovarian tuberculosis, uterine affections, undescended testicle), 
the affected animals manifesting . (uterine, ovarian, orchitic 
psychoses) an exaggerated sexual desire (nymphomania, satyriasis, 
erotomania, rutting, sexual insanity). 

There are, too, a number of vague nervous conditions which 
lead to perversions of taste (perversions of appetite) manifested 



Psychic Disturbances; Motor Disturbances. 427 

in animals, especially by the group of symptoms known as 
"licking" or pica (wool-eating sheep), the animals showing 
an inexpressible desire to lick all sorts of objects, even nauseat- 
ing substances, and to eat them ; an ultimately fatal cachexia 
developing in the chronic forms of these morbid appetites. 
[Analogous to the pica of chlorosis and other anaemias in man, 
and the dirt-eating habit of the anaemic hosts of uncinaria ; 
probably many cases in animals are really expressions of a simi- 
lar parasitism.] In rabid dogs there is a strong tendency to 
swallow foreign bodies. In sows the habit of eating the pigs and 
in ruminants of devouring the placenta are expressions of psychic 
abnormalities. 

(For fuller details see Friedberger-Frohner, Veterinary Pathology, 
Amer. Ed., 1904. W. T. Keener & Co., Chicago.) 

Motor Disturbances. — Muscular movements are normally — 
1, Voluntary, stimulated by the psycho-motor elements of the 
gray cortical substance of the brain ; 2, automatic, caused by chem- 
ical stimuli, independently of voluntary influence, occurring 
rhythmically and at all times present; 3, reflex, performed 
unconsciously and caused by transmission of sensory excitation 
to the motor' apparatus ; 4, co-ordinated and combined, the rapid 
succession and repetition of voluntary and involuntary move- 
ments as group actions, represented by facility of movement 
acquired from practice (Samuel). Disturbances of movement 
(motility) depend either upon pathological changes in the mus- 
cles, tendons, bones and joints, or upon changes in the motor 
nerves. The motor tract begins in the large ganglionic cells of 
the central convolutions, passes by the long pyramidal fibres to 
the cells of the anterior horns of the spinal cord and thence pass 
peripherally by the nerves distributed to the muscles. In addition 
those fibres and cells of the cerebral cortex which are concerned in 
perception, ideation and volitional stimulation are more or less in- 
volved in the production of voluntary movements. The complicated 
and widely distributed tract may be exposed at any point in its 
entire length to influences which are capable of interfering' with 
its functions. Such disturbances manifest themselves either as 
pathological exaggeration or pathological impairment of motility. 

Pathological exaggeration of motility is manifested by spasms; 
spasm or hyperkinesis (y Ktp-qais) may be defined as a paroxysmal 
muscular contraction which is occasioned by pathological stimu- 
lation or which, if caused by ordinary stimuli, exceeds normal 






428 Nervous Disturbances. 

degrees of contraction. When the members of the body are 
thrown into motion by these contractions alternating with relaxa- 
tion the spasm is said to be clonic (6 k\6vos , violent movement) or 
alternating; when the contraction persists for a longer time, 
causing maintenance of rigidity in one position, it is said to be 
tonic (6 tovos. tension). Tonus and clonus may succeed each 
other alternately. The mildest form of spasm is tremor, really 
a quick succession of contractions of single muscles or muscle 
groups, the coarser types evident as visible and palpable jerkings. 
These muscular contractions or spasms are spoken of as convul- 
sions when they give rise to excessive movement of the body 
and limbs, or violent tremors of the whole body (Samuel). Tonic 
spasm of individual muscles or of only one group of muscles is 
also termed a cramp (as of the jaw-muscles, trismus, from rpt'fw, 
to grit) ; the powerful and long continued contractions of the 
greater part of the musculature, tetanus ( reive* , to strain) ; a 
general body rigidity, without any important contraction (merely 
the ordinary contraction to maintain position), catalepsy; long- 
continued shortening of individual groups of muscles, with perma- 
ment deformity as a consequence, contracture (distinguished as 
active, spastic or reflcxophile in distinction from the passive con- 
tractures not of nervous origin met in disease of joints). Convul- 
sions when accompanied by loss of consciousness are described 
as epileptic or epileptiform. 

We know in connection with the causes of spasms that they 
may be induced by a group of poisons or chemical irritants 
(tetanotoxine, strychnine, ergotin, lead, carbonic acid gas), and 
may be produced by poisonous substances arising as metabolic 
products in the body (in uraemia), and that muscular contrac- 
tions may result (directly or reflexly) from mechanical excitation 
(section, torsion, crushing). In certain instances the spasms 
are caused by local lesions of the peripheral nerves, of the cord 
or of the brain (focal lesions), as the convulsions of suffocation 
by lack of oxygen supplied to the medulla oblongata, those of 
tetanus by the chemical combination of the toxine with the 
nervous substance of the spinal cord. The more minute lesions 
which take place in such examples are as yet not known, and the 
extremely confused ideas we possess of the relations between 
processes of excitation and inhibition prevent, for the present, 
any satisfactory explanation of the conditions involved. 

The results of spasms vary with the location of the causa- 
tive influence in the system. When the cause is directly in the 



Motor Disturbances. 429 

muscles the effects of the spasms are of little importance, except 
that in long standing contracture atrophy is likely to develop. 
Spasm of the respiratory muscles of necessity causes fatal suffo- 
cation because of interference with respiratory movements. 
Spasms of the muscles of mastication cause starvation. In other 
examples a fatal termination may be explained by the primary or 
seme collateral action exerted by the poisons causing the con- 
vulsions, the tetanus poison for example acting both by the 
lesions induced in the ganglionic cells and by a hemolytic action. 
It should be kept in mind that the spasms themselves are noth- 
ing more than the symptoms of the actual nervous disturbances. 

(For details v. Friedberger-Frohner, Lehrbuch der klinischen Unter- 
suchungsmethoden f. Tierarzte, III. Aufl. Stuttgart. F. Enke.) 

Loss of muscular power is termed palsy (akinesis [a. priv.,] 
ijKivrjaLs, movement) and may be differentiated into a complete loss of 
mobility (paralysis), or partial loss (paresis) in which the power 
of the muscles to perform movements is only reduced in degree. 
In case of deficiency in co-ordination, where the movements are 
performed clumsily and hesitatingly, the term ataxia ( a priv., 
77 t&£is, arrangement) is employed. Loss of motion occurs in 
pathological changes which directly inhibit muscular contractility 
(atrophy, inflammation, rupture, degenerations), or interfere with 
the movements of the bones (ankylosis of joints), or in conditions 
of inefficient innervation which induce palsy both indirectly by 
reducing the stimulus for contraction and by causing local 
changes [in the muscle]. 

A faulty innervation itself is usually the result of anatomical 
changes involving the ganglionic cells or nerve fibres and thus 
interfering with the formation of impulses or interrupting their 
transmission, as for example stretching, disintegration of the 
nervous substance by pressure (tumors), or destruction and degen- 
eration from poisons (toxines, lead), or disturbances of blood sup- 
ply. The location of the changes may be in the central motor 
apparatus, cerebral cortex or cord (cerebral or spinal palsy), or 
in the nerve trunks and their terminations (peripheral palsy). 

The central and some of the peripheral palsies are usually 
unilateral (hemiplegia) because they are usually due to focal 
lesions, to local changes, in one of the bilaterally placed nerve 
ganglia or nerves; while spinal palsies generally involve both 
sides of the body (paraplegia) because in the comparatively small 
transverse area of the spinal cord the lesion causing the anatomical 



430 



Nervous Disturbances. 



changes is apt to occupy the whole extent of the transverse section 
(transverse spinal palsy). 

Inhibition of the motor centres may also be caused by exces- 
sive stimulation of the sensory nerves in a reflex manner (so- 
called reflex paralysis or neurolytic palsy), as where complete 
paralysis of the posterior part of the body occurs after forcible 
compression of the kidney, bladder/ ureter or a portion of the 
bowel (Samuel). 

Results and terminations of palsies. The results of motor loss 
vary with the duration, extent of disturbance, the importance 




Fig. 131. 

Paralysis of the posterior part of the body ; transverse spinal palsy. 

by Dr. Jakob.) 



( Photograph 



of the affected muscles and of the causative lesion. In paralysis 
of the heart and respiratory muscles death at once ensues from 
cessation of circulation and gas interchange. Indirectly palsies 
of the pharyngeal muscles, the bladder, the intestine or the 
extremities may result in death because of the development of 
various possible complications (aspiration of fluid in the air 
passages causing aspiration pneumonia ; retention of urine and 
fecal material with production of dilatation, inflammation and 
erosion of the mucous membrane ; hypostases and decubitus with 
blood poisoning, etc.). In case of paresis of the sphincter of the 
bladder the urine constantly dribbles and the same symptom con- 



Sensory Disturbances. 431 

stantly occurs with palsy of the sphincter and detrusor muscles ; 
when the detrusor alone is paralyzed and the sphincter is intact the 
urine collects in the bladder. Paralyses due to destruction of 
ganglion cells are irreparable ; but peripheral palsies may some- 
times recover by regeneration of nerve fibres. When regenera- 
tion of nerves does not occur in the spinal palsies due to destruc- 
tion of the gray matter and anterior nerve roots, the paralyzed 
muscles undergo atrophy and degeneration, with rapid loss of 
electrical irritability. In case of central palsies atrophy does 
not occur (Samuel). 

Sensory Disturbances. — The sensory nerves transmit pres- 
sure and temperature sensations, special sensations (smell, 
taste, sight, hearing), and the so-called general sensations 
(hunger, thirst, special cutaneous sensations, sense of position). 
It is assumed that just as for the special senses there are par- 
ticular nerves, there are also for every other sort of sensation 
special nerves ; and it is known that nerves sensitive to pres- 
sure, pain, cold and heat have entirely specialized and character- 
istic endings (v. Frey, Krehl). From these local receptive end- 
organs the sensation is conveyed centripetally to the perceptive 
psycho-sensory parts of the brain, where proper distribution is 
made to the tracts and innumerable connections occur with the 
reflex and automatic nerves and ganglia. Disturbances of sensation 
may be considered as of two types, pathological excitation and 
pathological depression of sensation. Pathological excitation of 
sensory nerves gives rise to symptoms of sensory irritation of 
the most varied forms and grades, according to the kind and 
position of the terminal organ and the lesions. Sensation of 
pain is caused by stimulation of the nerves of pain, which are 
distributed in profusion and have their terminations in the skin, 
at the mucous membrane orifices, serous and synovial mem- 
branes ; these peripheral parts of the body therefore being capable 
of manifesting the most severe attacks of pain. Mechanical, 
chemical and thermic stimuli induce this symptom. If the 
nerve be in a condition of exaggerated irritability (hyperes- 
thesia) ordinary physiological variations (muscular action, ten- 
sion of tissue, congestion) are sufficient to bring on pain. Cer- 
tain forms of pain apparently develop spontaneously (neuralgia), 
that is, without demonstrable anatomical lesions and from unknown 
changes. The tracts extending from the muscles, bones and 
glands and into the central nervous system are less sensitive to 
pain ; although painful symptoms may be noticed arising from 



432 Nervous Disturbances. 

such locations also, as in affections of the spinal cord. In the 
brain, as indicated by the absence of pain during operative pro- 
cedures, the sensibility to pain is very low, at least in the cortical 
areas. Only hairs, hoof, and cartilage, provided the matrix be 
not also involved, are entirely devoid of the sense of pain, be- 
cause of the absence of nerves from these structures. 

The existence of pain is shown in animals partly by general 
symptoms (restlessness, pawing, stamping, running about, roll- 
ing over, groaning, sighing, gritting the teeth, whining and cry- 
ing shrilly), partly by local symptoms which suggest and more 
or less clearly indicate the location of the painful trouble 
(scratching, hobbling, protective movements when touched, strik- 
ing against the abdomen, looking around toward the posterior 
part of the body, arching of the back, symptoms of colic). 

Itching, indicated by the tendency to scratch, is met in cuta- 
neous affections, in some intoxications and general disturbances : 
it must be due to an irritation of the nerve endings (pressure 
points, Krehl), but the mode of origin is unknown. 

The irritative symptoms, "formication," "going to sleep" of 
some part, which are caused by pressure upon nerve trunks 
(paresthesia), light and color phenomena from irritation in the 
optic tract (photopsia, chromopsia) , abnormal temperature sen- 
sations, cannot be determined in animals, as they are subjective 
perceptions. 

Pathological diminution of sensation. In lesions which inter- 
rupt the course of the nerves at any position or render function- 
less the parts subjected to irritation, sensation is entirely lost 
or diminished or its transmission slowed. Sensory palsy (anes- 
thesia) may be induced by traumatic destruction of continuity 
(nerve section, crushing), by freezing, cauterizing the endings, 
by local anaemia, cedema, degeneration or atrophy of the peripheral 
nerves or brain and cord segments, as well as by the local and 
general action of certain medicaments (anodynes and anaes- 
thetics, as morphine, chloroform, ether, chloral hydrate). Paraly- 
sis of sensation may be total, so- that practically every kind of sen- 
sation is lost ; or it may be partial, as when the sense of pain is 
abolished and the pressure sense or sensitiveness to electrical irri- 
tation is retained, or where the special senses are destroyed but the 
sense of pain is intact. 

The results of disturbed sensation depend upon the impor- 
tance of the physiological functions abolished, Anaesthesias of 



Sensory Disturbances. 433 

the optic system cause visual weakness {amblyopia) or com- 
plete blindness {amaurosis). Anaesthesias of the auditory nerves 
produce nervous difficulty of hearing {hypacusis) or com- 
plete deafness {anacusis). Loss of the sensory power of periph- 
eral nerves is sometimes a source of danger for the tissues 
(for "the senses are the guardians of health"), which become 
conscious of every injury from the stimulus of pain and are thus 
able to call into action every protective means and measure the 
body possesses. In anaesthesia of the conjunctiva the entrance 
of foreign bodies to the eye or conjunctival sac is not realized, and 
such substances are not carried off by the flow of tears. After 
section of the sensory nerves of the foot, penetration of a nail into 
the frog is not evinced by lameness, and the ensuing inflamma- 
tion and gangrene of the hoof proceed unnoticed — conditions of 
serious ' consequence to the life of the subject. Interruption 
of the sensory portion of the reflex arc puts an end to the tendon 
reflexes, which cease in anaesthesia of the peripheral nerves because 
the path of conduction to the reflex centre (pyramids) is broken. 
If, however, the latter be intact and the communication between 
the brain and ganglion be destroyed the tendon reflexes are ex- 
aggerated (central inhibition may also exist). (Krehl.) 

Loss of the so-called motor senses destroys the coordination of 
movements and causes the appearance of symptoms of vertigo (v. p. 
424). The sense of station of the limbs, which renders possible the 
acts of walking, standing and especially of orientation in space, 
depends upon coordination of the optic and auditory organs, and 
especially those portions of the latter enclosed in the petrous por- 
tion of the temporal bone, as well as of the centripetal sensations 
from the muscles, tendons, bones, joints, fasciae and skin. 

Where there is loss of a single sense, as that of sight, orientation 
may be possible from increased acuteness of other senses (tactile 
sense, hearing) up to a certain degree. Loss of sensory muscle im- 
pulses or deficient transmission of these impulses or anaesthesia 
of the cerebral or spinal centres cause more or less loss of power 
of bodily motion. Disturbances of equilibration o\ the body occur 
especially in diseases of the organs in the semicircular canals, in the 
saccule and utricle, as well as of the central communications of these 
structures with the cerebellum. Mow far in these instances we have 
to deal with a pathological stimulation or paralysis, whether there 
exist a destructive phenomenon or one caused by deficient transmis 
sjon of impulses, are questions difficult to decide because of the 



434 Nervous Disturbances. 

complexity of the nervous mechanism and even more because of the 
great variety of processes and causes possible in case of such dis- 
turbances. 

Trophic, vasomotor and secretory disturbances depending upon 
nervous influences. — Of the vast number of cells which make up the 
animal body, there are, it is true, some cells, which are independent 
of the nervous system, acquiring their nutrition and performing 
their function by means of their own parenchyma alone. These are 
the isolated blood cells and lymph cells. All the other cells and tis- 
sues, however, in the matter of their metabolism, growth and main- 
tenance of existence, depend upon the nervous system; and die if 
they be separated from it. The part played by the nerves in this 
connection is known as the trophic influence. This is most clearly 
apparent in nerve fibres themselves, which invariably degenerate if 
divided from their ganglia or if the latter be the seat of disease. In 
warm-blooded animals disintegration in the form of fatty degenera- 
tion sets in as early as from four to six days. A nerve fibre may 
be looked upon as the elongated process of a ganglion cell, and in 
this conception disintegration is easily understood when it is re- 
called that, as taught by Verworn and Krehl, any part of a cell 
which' has been separated from its nucleus is sure to die. There is. 
it is true, a certain degree of individuality of the different segments 
of the nerve fibres so far as concerns their nutrition, metabolism and 
diseases, but permanent maintenance of their integrity is only as- 
sured by their continuity with the ganglion cells. And reversely the 
central portions of a neuron (that is to say, the ganglion cell) suffer 
if their connection with the peripheral nerves is broken ; for example, 
after section of a nerve atrophy of the central portion also occurs, 
perhaps extending to the ganglion. It is recognized that the integ- 
rity of the ganglia and nerves is dependent upon the exercise of 
their function, that functional stimulation is essential for mainte- 
nance of their nutrition and life. Atrophy usually appears in the 
voluntary muscles as soon as they lose„the influence of their proper 
ganglion cells in the anterior horns of the cord or of the equally 
important cerebral parts ; that is, when these become diseased or the 
communicating paths are interrupted or injured. The muscles, there- 
after incapable of voluntary movements, are thus rendered immobile 
(inactive, or paralyzed), become decreased in volume from diminu- 
tion in size of their individual fibres (simple atrophy, atrophy from 
disease), or may perhaps undergo granular and fragmentary disin- 
tegration of their contractile material (degeneration atrophy) ; a 
rapid shrinkage resulting, and'transformation of the muscle into flat, 



Trophic, Secretory and Vasomotor Disturbances. 435 

thin bands of fibrous connective tissue. To what degree this 
atrophy may be due simply to the motor inactivity or is dependent 
upon a loss of proper nutritive influences as the principal factor is 
not certain. In simple disuse of muscles, as that obtaining" in case 
of disease of the joints and bones or artificial fixation, atrophy may 
not appear for a long time, and the structure and electrical irrita- 
bility remain unchanged, because the motionless muscle is still in 
connection with its unaltered ganglion cell, performs other functions 
as heat production and metabolism, and continues to receive impulses 
of various kinds. In a neuropathic paralysis, however, the muscle 
no longer receives stimuli from the nerves and its metabolism no 
longer is as active; and atrophy may set in as early as within the 
first week after the nerve lesion, and may be so marked that in the 
course of a month the muscle may be reduced to half its former 
thickness. From these considerations it is evident that not mere 
inactivity alone, but the loss of some special trophic relation between 
the nerves and muscle, determine the issue. 

The most common example of such neuropathic atrophy is seen 
in the shrinkage of the posterior crico-arytenoid muscle in laryngeal 
hemiplegia (laryngeal wheezing in the horse). 

(For details v. Friedberger-Frohner, Veterinary Pathology, Amer. Ed., 
W. T. Keener & Co., Chicago ; Dexler, Die Nervenkrankheiten des Pferdes, 
1899 (Denticke's Verl.) ; Thomassen, Monatsheft f. prakt. Tierhcilkunde.) 

In the same way in case of disease or loss of continuity of the 
nerves nutritional disturbances develop in the bones (rarefaction, 
atrophy), the salivary glands and testicles (diminution in size, de- 
generation of the parenchymatous cells). The effect of castration 
upon the development of the body and the change of physical habit 
is presumably also to be attributed to some trophic influence of the 
nervous system. 

Secretory disturbances resulting from nervous lesions conform 
closely to the known physiology of glandular activity. It is well 
known that by direct or indirect stimulation of the secretory nerves 
of the salivary glands (facial nerve, gustatory nerve, trigeminus 
and branch of glosso-pharyngeal ; stimulation by digitalin, pilocarpin, 
or inflammation) an increased, sometimes permanently increased, 
secretion of saliva results. Similarly a flow of tears is induced by 
stimulation of the lachrymal nerve, cervical sympathetic, trigeminus, 
and, too, rcflexly by irritation of the nasal mucous membrane'. 

Vasomotor disturbances (angioneuroses) manifest themselves by 
abnormal dilatation or constriction of the vessels, the former deter- 



436 Disturbances of Digestion. 

mining a hyperemia, the latter an anaemia of the organ affected. 
Centres for the vascular nerves are located in the floor of the fourth 
ventricle, in the dorsal and lumbar cord and in the ganglionic and 
nervous plexuses which regulate the tone or ordinary state of con- 
traction of the arteries and the dilatation or constriction of the ves- 
sels to any calibre, and which are located about the walls of the ves- 
sels themselves. Stimulation of the fibres regarded as vasoconstric- 
tor causes diminution of calibre, anaemia and lowered temperature 
of the organ involved ; afterwards passing into paralysis, from 
which dilatation results. Paralysis of the vascular nervous centres 
also induces dilatation of the vessels and rapid lowering of blood 
pressure (section of cord, paralyzing poisons). Stimulation of the 
vasodilators causes marked dilatation of arteries, capillaries and 
veins and is induced especially by local toxic influences. 

Disturbances of Digestion. 

Diseases of the mouth, tongue, jaws and teeth all interfere with 
the taking of food and with mastication as well as the insalivation 
of the food within the mouth. The supply of nutritive material is 
thus diminished according to the grade and duration of such faults, 
and conditions of failure of nutrition and starvation are brought 
about. As the secretion of the gastric glands is in reflex associated 
relation with the movements of chewing so as to insure the imme- 
diate bathing of the swallowed bolus in proper juices (Pawlow), it 
is to be expected that in case of insufficient mastication the food 
taken into the stomach will be provided with a deficient amount of 
gastric juice and will therefore of necessity remain a longer time 
in the stomach. 

The movements of mastication mechanically cleanse the mouth of 
its mucus and bacteria (immediately after prolonged chewing of 
food the mouth is almost aseptic) ; anything which causes diminu- 
tion of these movements favors marked accumulation of micro- 
organisms, as a result of which acid fermentations take place in the 
mouth, facilitating decay of the teeth, accumulation of tartar on the 
teeth, pharyngeal catarrh, etc. 

In various diseases of the mouth (as foot and mouth disease), 
in a number of toxic disturbances (mercurialism) and nervous affec- 
tions (trigeminus), there ensues from direct or indirect nervous 
irritation an increased flow of saliva, the secretion dribbling from 
the mouth (salivation, ptyalism). Dribbling of saliva may also be a 
symptom of paralysis of the lips, 



Diseases of Pharynx, (Esophagus and Stomach. 437 

Diseases of the pharynx and the adjacent structures may, on the 
one hand, give rise to faults of obtaining food (painful inflamma- 
tions), and on the other hand if swallowing is interfered with by 
such conditions important complications may arise as consequences. 
As the respiratory and alimentary canals cross in the pharynx and 
the epiglottal orifice must be closed in the act of swallowing and the 
nasal cavity must also be shut off from the mouth by the superior 
pharyngeal wall, there arises a danger in all affections which dimin- 
ish the contractile power of the musculature of the pharyngeal walls 
(peripharyngeal cedema, inflammations, etc.) that particles of food 
and saliva may find their way into the nose or into the larynx and 
lungs. Sometimes the food and drink runs back (regurgitates) into 
the nose, or in case of pharyngeal palsy remains in the pharynx 
itself ; and under such circumstances drops and particles of the 
pharyngeal mucus and food may be drawn into the respiratory pas- 
sages (aspirated). The fluids of the pharynx and mouth are apt 
to contain great numbers of bacteria, and these foreign agents may 
cause in the lungs the most serious inflammatory disturbances, ter- 
minating in gangrene {gangrenous inhalation pneumonia) . 

Diseases of the Oesophagus may cause important interference 
with nutrition. Both by constrictions and, too, by patholog- 
ical dilatations of the gullet the food is prevented from passing 
regularlv into the stomach. The larger fragments lodge at the 
place of stenosis and in any dilated parts, or in case of paralysis 
lie stagnant in the lumen of the tube and block the passage. 
This induces retching movements (antiperistaltic contractions) 
on the part of the oesophageal musculature, or if the oesophageal 
muscles are paralyzed vomiting movements on the part of the 
stomach (pressure by the stagnant mass and by the oesophagus, 
stuffed full like a sausage, upon the vagus nerves). Further- 
more these stagnating masses of food undergo fermentation, 
cause injury to the mucous membrane and may in this way lead 
to rupture of the oesophagus ; and in the latter event, from 
escape of septic materials, the surrounding tissue (cellular ^is- 
sue of neck, mediastinum and thoracic cavity) is apt to undergo 
suppuration and gangrene. In ruminants from partial or com- 
plete obstruction of the oesophagus (new growths, pressure from 
enlarged mediastinal lymph nodes) regurgitation of the gastric 
contents and eructation of gases from the stomach are interfered 
with, with the resultant development of chronic flatulence. 

Diseases of the Stomach. — The efficiency of the gastric func- 



438 Disturbances of Digestion. 

tion is disturbed in two ways in disease, the gastric secretion be- 
ing affected in the first place and in the second the gastric motility 
being more or less affected. Usually both factors are involved 
at the same time, being directly or indirectly dependent upon 
each other. Disturbances of secretion are for the most ' part 
characterized by such features as diminution of the gastric juice, 
decrease in the proportion of acid (subacidity) and of pepsin 
resulting from degeneration of the glandular epithelium in acute 
and chronic catarrhs, anaemia, etc., or by continuous secretion of 
gastric juice without intervals of rest (caused by local inflamma- 
tory stimulation of the nerves of the mucous membrane). In 
the latter condition the secretion is apt to be poor in its hydro- 
chloric acid and peptic enzyme, and its increased volume accounted 
for by hypersecretion of mucus. The secretion under such cir- 
cumstances is likely to be of diminished functional value, or to be 
entirely incapable of digestive action, such a condition being 
termed dyspepsia. Although the passage of the gastric contents 
into the intestine is the principal factor in preventing serious 
prevalence of bacteria in the stomach, the acid of the gastric juice 
has a part in restricting the growth of bacteria and the occurrence 
of putrefactive changes in the viscus. A gastric juice poor in acid 
must be decidedly diminished in its antiseptic action, and for this 
reason a number of types of bacteria grow luxuriantly in the 
stomach in dyspeptic conditions. The gastric contents are often, 
in these instances, found to be neutral or alkaline in reaction, and 
putrefactive fermentation is present; where in spite of deficiency 
of hydrochloric acid an acid reaction prevails {dyspepsia acida), 
this is due to the formation of acetic acid (from alcohol, yeast 
fermentation) and lactic and butyric acids (from glucose, through 
the activity of bacteria). 

In other cases there may exist a hypersecretion with excessive 
hydrochloric acid production, or the latter (hyperacidity) may 
obtain without any increase in the digestive fluid (as a result oi 
special conditions of irritation), with the effect of inhibiting starch 
digestion and causing gastric pain and vomiting (Krehl). 

The products of fermentation and putrefaction of the gastric 
contents act as toxic irritants upon the mucous membrane, and 
may occasion further degenerative and inflammatory changes in 
that tissue. Under these and other circumstances, which induce 
(whether from circulatory disturbances or from the local lesions 
and toxic influences) paralysis or weakness of gastric peristalsis 



Diseases of the Stomach. 439 

{gastric atony), the churning and mixing of the gastric contents 
with the secretion are not thoroughly accomplished. When the 
ingested matter is thus inefficiently dealt with the undigested 
material is apt as a result to remain stagnant in the viscus, and 
this in turn favors increased fermentation and putrefaction. As 
gases are very likely to be present among the products of these 
processes, flatulence of the stomach (meteorism, from fxerewpLfriv, 
to inflate) may be expected, varying in its intensity ac- 
cording as to whether the gas finds its way through the pylorus, 
is absorbed or finds an outlet through the gullet in belching, or 
whether it fails to escape. 

Delay in emptying of the stomach or retention of the contents 
favors gastric dilatation. A distended stomach because of its 
increased volume causes pressure influences upon the adjacent 
parts, compresses the liver, vena cava, etc., interferes with the 
diaphragmatic movements and thus renders respiration difficult. 
Even in moderate degrees of distension the absorptive powers 
of the gastric mucous membrane is diminished because of the 
tension of the lymphatics and blood vessels. The distended wall 
of the stomach may rupture and fatal haemorrhage from the torn 
blood vessels quickly terminate life. Digestive faults in the first 
stomach of ruminants occur in the same general way as above, 
but with the difference that there is here no secretion from the 
gastric mucous membrane and we have to consider merely the 
macerating properties of the fluid swallowed, mixed with saliva. 
In these animals accumulation of gas and tremendous distension 
invariably occur, either suddenly or gradually, when the con- 
tractile power of the wall of the paunch is lost. This may be 
caused by a number of influences, as chilling of the mucous sur- 
face of the paunch by frozen or rain-drenched food, overfeeding 
or overwork without allowance of time for rumination, or toxic 
substances capable of causing paresis of the gastric wall and met 
in various food stuffs, as lucerne or clover. Meteorism may also 
be noticed when belching of gas is prevented by constrictions of 
the oesophagus. 

Exaggerated gastric movements occur especially in connection 
with pyloric obstruction, or from the influences of chemical ma- 
terials which directly irritate the mucous membrane of the viscus 
or the smooth muscle of its walls, or may be caused indirectly 
by influences acting on the medulla oblongata (reflexly and by 
irritation of the vagus). The violent contractions of the muscle 



440 Disturbances of Digestion. 

of the organ may cause it to be rapidly emptied into the intes- 
tine, or, in association with the muscles of respiration (spasmodic 
contraction of the muscles of the abdominal wall and diaphragm), 
may cause vomiting (vomitus) . It may be safely assumed that, 
as in man, more or less gastric pain is caused also in animals by 
various affections. Distension of the stomach, the marked stretch- 
ing of the wall, give rise to a sense of pressure ; and the local 
effects of poisons, of increased proportions of acid, and of toxic 
bacterial products upon the sensory nerve fibres of the mucous 
membrane, and especially the occurrence of spasms of the gastric 
muscles, must surely often cause intense pain. It is known that 
in man migraine and vertigo as well as epileptiform convulsions 
may be of gastric origin, apparently from vagus irritation ; and 
some of the nervous symptom groups, as distemper of dogs, may 
perhaps be explained by gastric changes. 

Diseases of the Intestines. — In all intestinal diseases the 
micro-organisms, which teem in the contents and cause all sorts 
of disintegrative changes in the material, play an important part. 
Bacteria of many types, yeasts and hyphomycetes, as well as in- 
fusoria, are to be found in the intestine of the healthy human be- 
ing and animal, being introduced with the food. Pasteur and 
Schottelius have pointed out that the presence of these com- 
mensualists is an absolute necessity for the herbiverous "animal, 
the bacterial processes being adjuvants in the digestion of the 
food (it has been impossible to keep alive chicks hatched in 
sterile surroundings upon artificially sterilized food) ; although 
voting guinea pigs have shown their ability to live and thrive on 
pure milk diet without bacteria in their intestine (Thierf elder 
and Nnttal). 

The harmlessness of the ordinary intestinal bacteria is due 
to the fact that the healthy epithelium of the gastric and intestinal 
mucous membrane acts as an impenetrable barrier against them; 
the protective means possessed by these cells being apparently 
their strongly acid, albumen precipitating nucleinic acids (Klenl- 
perer). Again it is possible that the intestinal epithelium, as well 
as the rest of the tissue in every individual, may become accus- 
tomed to the toxic products of the ordinary intestinal bac- 
teria, just as the epithelium of the stomach and upper part 
of the intestine is acid proof ; or it may be that an immunity 
is obtained by the formation of antibodies. Then too the 
acid gastric and small intestinal juice, as well as the bile, 



Diseases of the Intestines. 441 

surely possess some degree of influence inhibiting the multipli- 
cation of the microphytes taken in with the food. Marked ex- 
cessive prevalence of bacteria is, however, mainly prevented by 
the comparatively rapid passage of the chyme through the small 
intestine and the discharge of large quantities of microorganisms 
periodically with the dejecta from the large bowel in regular 
defecation. 

In conditions which interfere with the normal passage of the 
chyme through the intestinal tract, as in stagnation of the intes- 
tinal contents from obstruction, strictures, etc., or where the 
epithelium of the mucous membrane has undergone changes 
(degeneration, necrosis, desquamation), even the ordinary in- 
testinal bacteria are capable of causing harm ; and this is obvi- 
ously possible where other types of microphytes having special 
toxic properties are introduced, these perhaps causing epithelial 
necroses or their toxic products being absorbed. We should re- 
gard, at any rate, as harmful products of ordinary intestinal 
bacteria the products of acid fermentation of the carbohydrates 
(lactic acid, butyric acid, acetic acid), these when present in large 
amount causing erosion of the mucous membrane (especially 
the delicate mucous membranes of young individuals), and gases, 
as hydrogen and methane and sulphuretted hydrogen, arising in 
albumen putrefaction. 

The metabolic products of the bacteria themselves are even 
more numerous and their influences varied. But little is known 
of their relation with the pathology of the intestine, and 
there is so much confusion as to the nature of these some- 
times poisonous substances, and their relation to the alkaloids, 
albuminates, enzymes, etc., that it is at present best to be satis- 
fied with their tentative classification into toxines and endotoxines. 
We can only speak in a general way of the bacterial processes in 
the intestinal canal as the source of pathogenic and fatal changes, 
and say that on the one hand they occasion local lesions like 
inflammations, haemorrhages or necroses, and on the other hand 
give rise to general intoxications. Similar effects may be pro- 
duced by the ingestion of various chemical substances (poisons 
taken in with the food). 

In many intestinal affections disturbances of the absorptive 
power of the mucous membrane ensue. This is especially true 
of the diffuse lesions; although in circumscribed changes the 
intervening portions of mucous membrane remaining unaltered 



442 Disturbances of Digestion. 

continue to act and to transmit as usual the sugar and albu- 
men to the blood and the fat to the chylous vessels. " The 
causes of impairment of absorbent power lie primarily in the 
alterations of the intestinal epithelium, which normally acts 
in fact by attracting the nutrient substance to it (Krehl), and in 
the second place in the disturbances in the lymph follicles of the 
intestine ; and, too, the passage of the intestinal contents may 
be too rapid to favor absorption, the period of contact of the 
nutrient material with the intestinal mucous surface being 
curtailed. The terms looseness of the bowels or diarrhoea are 
applied to the accelerated passage of the chyme through 
the intestine, apparent from the fluid or thin intestinal dis- 
charges. The usual cause of this condition is a heightened peris- 
taltic action of the intestinal musculature ; which may prevail 
throughout the intestinal tract or be restricted to the large intes- 
tine, and is due to irritation of the sensory nerve filaments in 
the mucous membrane, with transmission of the impulse to the 
motor nerves of the intestinal muscles. According to Cohnheim 
extensive and general movements of the intestine can be aroused, 
starting from any level of the gastrointestinal canal, by merely 
moderately strong irritation. Hand in hand with the increased 
movement hypersecretion from the mucous membrane may take 
place, a transudation from the blood vessels, as another effect 
of local irritation. The irritant substances are of innumerable 
chemical types, including materials ingested from the outside of 
the body (drastic purgatives) or decomposition products formed 
in the bowel itself. According to Krehi the organic acids and 
gases (carbonic acid, hydrogen) are especially efficient in stim- 
ulating intestinal movements. When the intestinal mucous 
membrane is already inflamed and hyperaemic even an ordinary 
amount of irritation is sufficient to cause increased peristalsis, as 
the nerves are even then subjected to pressure from the distended 
blood vessels and transudate (Cohnheim) or are deprived of 
their protective covering because of the defects in the mucous 
membrane. Diarrhoeas may also be caused, however, by 
prevention of absorption of water from the intestine, which 
may be the case when salines are present in the gut, these sub- 
stances having a strong tendency to combine with water and 
being themselves difficult of absorption (saline laxatives). Sud- 
den changes of the blood currents and the blood gases, soaking 
or chilling the skin, or putrid blood poisoning are also factors 



Diseases of the Intestines. . 443 

which directly or indirectly are liable to cause spasmodic contrac- 
tions of the intestinal muscles (dysperistalsis). 

As already stated the absorption of nutritive material is dis- 
turbed in diarrhoeas ; but in addition the digestive secretions and 
the digestible constituents of the food are carried out of the body 
by the frequent dejections. Besides there are losses of the 
epithelium of the mucous membrane, losses of the inflammatory' 
albuminous transudate or of blood; so that the body suffers also 
a loss of its circulatory and organic albumens. For these reasons 
diarrhoeas weaken the strength of the subject, bring about a 
state of inanition and may perhaps be, fatal. Although resorption 
is reduced in diarrhoeas it is not entirely checked, being main- 
tained in this or that segment of the bowel; because of this it is 
possible, in addition to the disturbances mentioned, that re- 
sorption of toxic substances may prevail, this feature adding 
complications to the morbid condition and aiding in bringing 
about a fatal termination. 

There are a variety of influences which may retard the pas- 
sage of the chyme or completely stop its movement. Infrequent 
defecation, protracted retention of the chyme in the large gut, 
obstipation or constipation (constipare, to render compact), or 
simple stoppage of the bowel, is usually due to the character of 
the food, which may cause the chyme to be too thick because of 
insufficient presence of water or which' does not stimulate the 
mucous membrane enough and causes an atony of the muscles of 
the intestine (from feeding bones to dogs, bran to horses). A 
constriction or complete closure of the intestinal lumen, stenosis, 
obturation or occlusion/ 1 ' may be due to presence of foreign bodies 
(enteroliths, concretions, swallowed stones, cork stoppers, etc.), 
to tumors or to cicatrices. Or the intestine may be compressed 
or squeezed from without (strangulation of intestine, incarcera- 
tion) when caught in some opening (rupture, hernia), or sur- 
rounded by some band ; may be twisted (intestinal twist, volvulus) ; 
or become impermeable because one segment becomes invag- 
inated in another (intestinal intussusception, invagination). The 
obstruction of the lumen in all such cases causes a retention 
of the chyme with accumulation toward the stomach, and the 
possibility of passage of the intestinal contents, both iood refuse 
and gases, to the anus is interrupted. The chyme stagnating 
above the obstruction, in which the processes oi bacterial decom- 

*Obstrucrc, to barricade, slop up; occludcic, to dose up; obturare, to divert, 
according to Roth, probably from Ovpa, door. 



444 Disturbances of Digestion. 

position are continually going on, distends the intestine, partic- 
ularly by gaseous inflation. If the lumen is merely narrowed and 
not completely obstructed and if the obstructing cause is slow- 
in development, a compensatory hypertrophy of the musculature 
may ensue (v. p. 255), and for a time overcome the difficulty; 
the strengthened wall by its more forceful contractions succeed- 
ing in forcing the fluid chyme through the narrowed passage. 
Where occlusion is sudden and complete, however, the retained 
contents accumulate in such amounts and the gaseous distension 
becomes so intense that serious symptoms and results are in- 
duced. The pressure, whether from without or from within the 
gut, upon the nerves of the intestinal wall and mucous membrane 
and their irritation by the chemical substances in the contents, 
cause violent contractions, spasms of the smooth muscles ; which, 
either by anti-peristaltic movements or because of mere disten- 
sion of the tube, and because from vagus irritation retching 
movements are set up, induce overflow and regurgitation of the 
chyme into the stomach, a process known as ileus (6 d\e6? t 
from eixiu), I close, or et'Xew, I turn, according to Roth) or 
miserere, because of the frightful torture which it causes. 
The violent muscular spasms of the intestine are accom- 
panied by severe pains, colicky pains or griping (ij KwKudj-, sup- 
ply vdsos ; from T 6 k&Xov, the colon), giving place to an intestinal 
paralysis due to fatigue of the muscular tissues and the stretch- 
ing of the wall from gas accumulation. The distension as well 
as the spasmodic muscular contractions may lead to rupture of 
the intestine, along with pressure upon the neighboring organs 
and the large blood vessels, of the abdominal cavity. The 
stretching of the nerve fibres (splanchnic) with its reflex effect 
upon the heart, the continuous vomiting and the absorption of 
toxic substances, make up a group of processes which, with rapid 
loss of strength, cause the death of the animal. In conditions in 
which strangulation of the bowel causes the occlusion there are 
added to the above phenomena disturbances of the blood cir- 
culation in the intestine, venous congestion, congestive haemor- 
rhages and transudates, and gangrene. Gangrene necessarily 
must result from the penetration of the intestinal bacteria into 
the tissues which are engorged with blood, without the least cir- 
culation and therefore necrosing. 

Diseases of the Liver. — The manifold functions of the liver 
make it easily realized that any affection of this organ which is 



Diseases of the Liver. 445 

associated with destruction of its secretory parenchyma or with 
disturbances in the entrance or exit of blood, should be followed 
by numerous reactive effects upon the general body. The chem- 
ical function of the liver does not extend merely to the production 
of bile and furnishing of glycogen, but is directed to the pro- 
duction of a large number of enzymes having for their purpose 
the dissolution, transformation, precipitation or complete de- 
struction of toxic material circulating through the blood, but 
brought to the liver especially from the intestine. The liver 
possesses, therefore, an antitoxic function, and is a toxolytic 
organ of the greatest importance. According to Bangger and 
Zschokke the following enzymes have been isolated from the 
liver or bile; maltase, glykase, a proteolytic ferment (similar to 
trypsin), nucleinic ferment, aldehydase, lipase, fibrin ferment, a 
milk curdling ferment ; and there have also been recognized a fer- 
ment capable of forming ammonium and urea from the amido 
acids, one forming glycogen from sugar or the reverse change 
(of sugar from glycogen), another forming iron and bilirubin 
from haemoglobin, and finally one causing the combination of 
cholic acid with glycocol and taurin, and of phenol with ethyl- 
sulphuric acid. A large number of alkaloids are rendered com- 
pletely or partly inert by the liver. Schiff proved experimentally 
that a dose of nicotine, which is fatal if injected into a peripheral 
vein, is without effect if injected through the portal vein, and 
that an infusion of nicotine made into an emulsion with fresh 
liver tissue loses its toxic properties, while if rubbed up with 
muscle or nervous tissue quickly evinces its toxicity. In the 
• same way strychnine, cicutine, veratrine, caffeine, atropine, curare 
and animal toxines, extracts from putrefied tissue, have been 
found to be less toxic if mixed with liver tissue or injected by 
way of the portal vein so that they must first pass through the 
liver. Roger has shown that the portal blood before coming to 
the liver contains a considerable amount of toxic substances 
apparently absorbed from the intestine; the blood of the other 
veins of the body, on the contrary, showing a far less toxic quality 
in spite of the fact that it carries with it various metabolic prod- 
ucts from the tissues. The intestine is a chemical laboratory in 
which a great quantity of bodies of the most varied character arc 
formed from the combination of the digestive juices with the 
food ; and then, too, the myriads of bacteria which inhabit the 
intestine give origin to products of more or less toxic nature. 



446 Disturbances of Digestion. 

Bile, peptones, ferments, various vegetable acids, gases, the in- 
testinal putrefaction substances, various alkaloids and proteid 
bodies are to be met; and are, it is true, largely carried out of the 
system with the feces, but to a certain degree are also absorbed 
by the portal venous radicles. The liver serves as a cleansing 
apparatus, and frees the portal blood from these harmful ingre- 
dients. As soon as the liver becomes affected by diseases which 
reduce its antitoxic functional ability, these substances must 
necessarily pass through the organ without being transformed and 
gain entrance to the general circulation and be changed possibly 
by other tissues or be eliminated by the kidneys, lungs and per- 
spiration. The kidney is particularly capable of acting in place 
of the liver in purifying the blood. It has been shown that the 
urine in hepatic diseases and in conditions which cause an in- 
creased albumen disintegration (whether in the liver itself or 
elsewhere) acquires decidedly increased toxic properties and 
contains instead of or along with urea large amounts of am- 
moniacal compounds or acid bodies, as amido acids (leucin, 
tyrosin), aromatic oxyacids, acetone and albumoses. Such ma- 
terials are, however, injurious to the kidneys and for this reason 
disease of the liver is frequently complicated by pathological 
changes in the kidneys. In case of failure of the compensatory 
function of the kidneys, and especially if poisonous substances no 
longer neutralized by the liver parenchyma are passing into the 
blood, there may ensue symptoms of general intoxication acting 
particularly upon the central nervous system. These phenomena 
may be met in varying grades of severity, as convulsive or stupor- 
ous conditions of acute or protracted course, according to the 
extent of destruction of liver cells, the increase of albuminous 
disintegration in the liver and the access of infectious factors. 
The most important poisonous material which occurs in case of 
destruction -of the hepatic function concerned in the transforma- 
tion of albuminates into urea and uric acid, is carbamic acid : the 
entrance of this material into the blood, as seen in animals de- 
prived of the liver or having an Eck's fistula (Minkowski*), causes 
very intense cerebral disturbances. 

Stagnation of bile, besides causing 'biliary staining of the liver 
and the rest of the body structures, the so-called icterus (v. p. 
212), is also responsible for cerebral toxic symptoms (spasms 
and stupor), because of complex conditions of intoxication simi- 

* For details see Kitt, Pathol. Anatomie der Haustiere, II Aufl. 1 Bd., p. 595. 



Diseases of the Pancreas. 447 

lar to the above. The cholic acid especially is toxic to the nerv- 
ous structures, but the biliary pigments are not entirely inert; and 
haemolysis also plays a part (cholcemia). Obstruction of bile 
from the intestine and, too, diminished or completely checked 
production of bile (oligocholia, acholia), because of degeneration 
of the hepatic parenchyma, disturb the formation of the chyme; 
absorbtion of fat is made difficult in the absence of bile and the 
loss of the antiseptic influence of bile may cause intestinal catarrh 
from putrefaction of the ingesta. 

Hepatic diseases also affect the nutrition of the tissues, from 
bringing about changes in the character of the blood. The liver 
is the storehouse for the sugar of the blood (E. Voit), which it 
elaborates from the material brought to it from the intestine by 
the portal vein ; it stores up fat, and consumes the debris of broken 
down corpuscles; and in case of loss of these functions the body 
must suffer from the abnormalities in some of its important 
sources of energy. Further there may be mentioned altera- 
tions which are brought about by mechanical interference with 
the blood circulation, as in diffuse induration of the liver; all dis- 
eases which tend to occlude the blood capillaries and cause com- 
pression and narrowing of the innumerable intrahepatic ramifica- 
tions of the portal vein bring about passive congestion of the 
organs in which the portal vein originates, the stomach, intestine, 
spleen, and the visceral portion of the peritoneum. From this 
condition, dropsical transudation, ascites, is apt to develop. 

Diseases of the Pancreas. — Diseases of this organ causing 
atrophic changes of the glandular parenchyma, render the 
formation and discharge (into the intestine) of its secretion 
impossible, have an important influence upon digestion of proteids 
and absorbtion of fats, may be followed by diabetes, and lead to 
serious and progressive emaciation. Especially in case of the 
horse, an animal possessing a relatively small stomach and only 
a short period of gastric digestion, the loss of the pancreatic func- 
tion cannot be compensated for by other glands and gives origin 
to a fatal cachexia (Siedamgrotzky). Observations on dogs, cats, ( 
hogs, rabbits, pigeons, birds of prey, after extirpation of the gland 
or restriction of its secretion from the intestine by ligature of 
the duct, have shown that in case of failure of the pancreatic 
juice fats are no longer absorbed (only in natural emulsion is 
fat absorbed to the extent of thirty to forty per cent. ; all the 
neutral fat reappears in the feces: and only part of the fats is 



448 Disturbances of Respiration. 

split) ; only about forty- four per cent, of the proteids are absorbed 
(Abelmann, Krehl), and sixty to eighty per cent, of the carbo- 
hydrates. The latter and the sugar formed within the body from 
the albumens are excreted unchanged in the urine (Minkowski). 
The diabetes thus produced varies in its severity according as to 
whether the gland has been completely or only partially removed 
in operation, whether it is generally involved by disease, or 
whether portions of the gland remain in functionating condition. 
In dogs and cats after total ablation of the organ, the urine 
usually contains as high as eight to ten per cent, of sugar ; and 
the animal may be expected to die from the progressive cachexia 
in the course of fifteen to twenty days. Diabetes fails, if, in ex- 
perimental removal, a sufficient amount of the gland is left or 
transplanted under the skin; and occlusion of the duct (ligature, 
obstruction by calculi) does not invariably cause diabetes, as 
the secretory substance may then be absorbed through the lym- 
phatics and be conveyed to the blood. The active agent involved 
is believed to be a ferment whose function is the destruction of 
the sugar in the blood ; if this be wanting the sugar necessarily 
accumulates in the blood and passes unchanged into the urine. 
It is of further interest to recall that in diffuse carcinomatosis of 
the pancreas diabetes may similarly be absent, apparently because 
the tumor cells, as the offspring of the secreting gland cells, are 
capable of carrying on the function of the latter to an extent suffi- 
cient for the metabolic demands in this direction. 

The effects of failure of the pancreatic juice to pass into the 
intestine may, in normal conditions of the intestine, be practically 
compensated (not in the horse — v. supra) by the fat-splitting 
power of the bile and the intestinal bacteria, the latter causing 
proteid putrefaction at the same time. 

Disturbances of Respiration. 

The constant intake of oxygen and output of carbonic acid 
gas is the first vital requirement of the cells of the animal 
body. In fcetal life this interchange of gases is performed by 
means of the placental circulation, in post-natal life by the en- 
trance of atmospheric air to the respiratory surfaces of the lungs; 
and the red blood corpuscles act as essential agents in causing 
the interchange. The inspiration of the atmospheric air and the 
output of that which has been rendered unfit, constituting what 
is known as the external respiration, may be impaired by closure 



Faults of External Respiration. 449 

and constriction of the respiratory passages, diminution of the 
respiratory surfaces of the lungs, and by any interference with 
the movements of the respiratory muscles. In conditions of ob- 
struction of the nasal passages (swelling of the nasal mucous 
membrane, tumors), breathing may for the time be still accom- 
plished through the mouth; obstruction of the larnyx and tra- 
chea with its branches, by foreign bodies 01 tumors in the lumen, 
spasm of the glottis, external pressure (thyroid tumors, oesopha- 
geal diverticula, strangulation), or collection of exudates in the 
tubes, causes difficulty of respiration (dyspnoea, air hunger) in 
proportion to the extent of the obstruction. Proportionately to 
the degree of diminution of entrance of air to the lungs the blood 
becomes impoverished in oxygen and its carbonic acid content 
increases. Lack of oxygen and excess of carbonic acid in the 
blood act to stimulate the respiratory centre in the medulla ob- 
longata (point of exit of the vagus) ; this stimulation, and prob- 
ably the mechanical influence of incomplete filling of the pulmo- 
nary alveoli, which directly affects the fibres of the vagus, bring 
about an increased contraction of the inspiratory muscles. In- 
spiration becomes stronger, more powerful, deeper and longer 
in duration, because the narrowed lumen of the tubes does not 
admit the external air to pass readily into the alveoli and the de- 
mand for oxygen in the medulla oblongata is not at once satis- 
fied (Krehl). The air becomes rarified in the lung and the in- 
tra-alveolar pressure less than the external pressure upon the 
outside of the body; and for this reason inspiratory retractions ot 
the intercostal tissues may be noted. Because the air cannot pass 
out through the narrowed portions of ftie tract with the usual 
ease, the lung does not collapse as rapidly as normally and ex- 
piration is also prolonged (Krehl). 

Contraction of the diaphragm is the main factor of the inspir- 
atory forces, the contraction of tin's broad muscular sheet, arch- 
ing anteriorly because of the pressure of the abdominal viscera, 
causes it to assume a flatter plane and thus increases the thoracic 
space, the elevation of the chest wall, especially the lower ribs 
(by the levator costarum muscles) aiding in producing this ef- 
fect. Expiration is due to cessation of the diaphragmatic contrac- 
tion (termination of its tension) and that of the levator muscles, as 
well as to the elastic contraction of the lung expanded in inspira- 
tion. Ruptures of the diaphragm (excluding here the question 
of haemorrhage from the ruptured blood vessels and hernia of 



450 Disturbances of Respiration. 

the abdominal viscera into the thoracic cavity) usually rapidly 
cause death because of the resulting impossibility of breathing. 
Difficulty of respiration is similarly occasioned by embarrassment 
of and pressure upon the diaphragm by meteorism of the abdom- 
inal organs, tumors, etc., where the alteration of contracting 
movements and resting stages is lost in consequence of tetanic 
spasm of the thoracic muscles and diaphragm. When air gains 
entrance to' one of the pleural spaces because of a wound of the 
thoracic wall or rupture of the lung (perforating wounds, rupture 
of suppurating foci), the lung affected contracts from the action 
of its elastic tissue and, because being no longer impervious to 
air, it must adapt itself to the intrathoracic conditions (the me- 
diastinum is pressed toward the opposite side by the entering air 
and may even be ruptured) ; expansion of the lung is, therefore, 
no longer possible, as the organ cannot follow the movements of 
the chest wall and lies loosely (that is, fixed only at its root) in 
the chest cavity. The thorax and lungs cannot properly expand 
and collapse if the chest cavities are occupied by fluid exudates 
(dropsy, pleurisy), or if the respiratory surfaces of the lungs are 
lessened, if a greater or less portion of the pulmonary alveoli are 
filled up or solidified by pressure of collections of exuded material, 
tumors or parasites and thus deprived of their air. However, 
even on the contrary if the lungs are excessively inflated, over- 
distended, a condition known as emphysema, aeration of the or- 
gans and interchange of gases with the blood are' impaired ; the 
lung not collapsing properly in this condition, the air escaping 
with difficulty (the carbonic acid is unable to pass out by dif- 
fusion to a sufficient degree), and the capillaries narrowed by 
being stretched and not permitting the blood to flow readily through 
their lumina. Under any such condition breathing becomes 
labored and air hunger becomes apparent. In addition circula- 
tory disturbances are induced, sometimes due to pressure upon 
the thin walled veins by accumulations of fluid in the chest cavity 
and by the uninterrupted enlargement of volume of the lungs, 
this causing congestion in practically all of the veins (v. dropsy) ; 
the factor of aspiration of venous blood fails ; and as terminal 
features difficulties of discharge of the blood from the right heart 
grow apace (resistance in pulmonary arterial area), if the vas- 
cular distribution in the lungs be embarrassed by pressure or 
obstructive influences (secondary cardiac hypertrophy and dila- 
tation)'. 






Respiratory Motor Disturbances. 451 

In some affections the respiratory movements are accelerated 
and more or less superficial. Increased frequence of respiration 
is met particularly in febrile affections and inflammatory affec- 
tions involving the bronchioles. The causes underlying rapid and at 
the same time superficial breathing are not understood; it is sup- 
posed that the responsible influences are related with the in- 
creased internal temperature or some irritation of the sensory 
vagus filaments. Respiratory disturbances may also be brought 
about by cerebral lesions. Affections of the nervous substance 
of the brain which do not induce paralysis of the medulla oblon- 
gata, accumulation of fluid, parasites, haemorrhages or toxic and 
infectious irritants, may cause an increase of intra-cerebral pres- 
sure, this apparently disturbing the stimulation of the respiratory 
centre, respiration becoming slowed even though the air is not 
in any way obstructed in its passage to the alveoli. 

When the inspired air contains poisonous gases, it is to be 
expected that according to the character of these substances and 
their quantitative admixture in the atmosphere there will be man- 
ifested either violent coughing or suffocative symptoms (ammonia 
for example) ; and inflammatory local disturbances will be induced 
(inhalation of formol vapor) ; or that some blood change (as in 
carbon monoxide poisoning) will be brought about by limitation 
of the atmospheric oxygen and alteration of the haemoglobin. 

The respiratory variations are the result of regulative pro- 
cesses set into activity automatically and reflexly by the respira- 
tory centre. Deeper or accelerated respiratory movements may, 
to a greater or less degree, compensate for faults of gaseous in- 
terchange of the blood and the tissues. With cessation of the fault, 
as by removal of an obstruction to the entrance of air to the lungs, 
and coincidently with the moment when the medulla oblongata 
again receives a proper amount of oxygenated blood, the special 
stimulation of the centre ends and the respiratory movements again 
become normal. Where the causes, however, continue operative 
and become more marked, and even the excited respiratory move- 
ments finally become incapable of relieving the air hunger of the 
tissues, asphyxia (suffocation) must ensue. As long as the brain 
retains its normal irritability the labored and deep respiratory 
efforts indicate medullary irritation, and in the latter case the 
rate of cardiac action is also slowed from the marked irritation 
of the vagus, and the cutaneous vessels are dilated because of 
irritation of the vasomotor center (Krehl); after a time tonic- 



452 Disturbances of Respiration, 

clonic convulsions occur and death follows after a short period of 
paralysis (Krehl). Where the irritability of the central nervous 
system is diminished (haemorrhages into the brain, increased 
intracranial pressure, toxic or infectious influences) the symptoms 
caused by diminution in oxygen supply are less violent ; the 
gradual and progressive increase of carbon dioxide produces a 
cerebral narcosis, the respiratory movements become gradually 
weaker and life ebbs away with the advancing paralysis of the 
central nervous organs (Krehl). 

The respiratory tubes are provided with a number of pro- 
tective mechanisms, which serve to remove foreign particles 
which have gotten into the air passages. The passage to the 
trachea and lungs leads over an area, the naso-pharynx, richly 
inhabited by bacteria and often the point of lodgment of foreign 
bodies; the narrow laryngeal opening is the threshold separating 
this septic territory from the tracheal system. Of course, the 
larger foreign particles which get into the nose and pharynx 
and which irritate the nerves of the mucous surface and thus in- 
duce sneezing and snorting, are from time to time discharged, 
and the entrances for air are kept free for the passage of air; 
but motile virulent organisms may easily pass in, and aspiration 
of small drops of septic mucus and saliva or even food particles 
may readily occur. In this case (these substances having passed 
into the trachea and bronchi) the continued activity of the ciliated 
cells serves to remove these foreign particles, carrying them back 
to the trachea and larynx. The mucus secreted over the whole 
surface of the tubes serves to envelop the foreign elements, and, 
too, dilutes the poisonous substances and renders them inert. 
Moreover, the numerous depots of lymphoid cells may make an 
efficient phagocytosis possible and thus facilitate the removal of 
very minute foreign particles. In addition the reflex production 
of coughing, which forcibly discharges foreign objects, the col- 
lections of mucus to which they are adherent and any other 
injurious contents of the trachea, is manifested and acts to cleanse 
the upper portion of the tubes. Excitation of cough is prin- 
cipally induced by local irritation of the sensory vagus fibres in 
the larynx and trachea, and may also originate in the pleura, a 
special group of movements of the respiratory muscles being ex- 
cited reflexly through the medulla oblongata. Cough begins with 
a deep inspiration, followed by a forcible expiration; the air under 
high pressure in the lungs forces its way out through the opening 



Coughing. 453 

of the opposing rima glottidis and drives everything in the larynx 
and trachea (to a certain extent, too, that which is in the pharynx) 
out into the mouth . (Krehl). Foreign bodies, exudates, etc., 
lodged below the bifurcation of the wind pipe may also at times 
be carried out ; but there is a chance that objects in this position 
may be driven deeper into the bronchial tubes (Krehl). Expec- 
toration, removal of such substances from the chest (or better, 
the lungs) is accomplished primarily by the ciliated epithelium 
and the upward convection, by this means, of the mucous vehicle; 
the stimulus to cough acting upon the expectorate (sputum) 
only from the level of the bifurcation upwards. 

These defensive mechanisms may be of no efficience if the 
harmful chemical, bacterial or mechanical agents are of such a 
character that they paralyze and destroy the epithelial cells and 
their ciliary action, and the phagocytes or the smooth muscles 
of the bronchial tubes, or if the foreign bodies are held firmly 
because of swelling of the bronchial mucous membrane, or if the 
obstruction be tightly fixed because of its size; and may be in- 
effective because of lesion or disease of the motor or sensory ap- 
paratus involved in coughing movements. The retention of for- 
eign bodies and pathological secretions may be followed by 
asphyxia, because of the obstruction to the air passages ; or may 
be the cause of such serious effects as gangrene of the lung, etc., * 
as the obstructing substances usually carry bacteria with them. 
(Under normal conditions the pulmonary alveoli, the bronchial 
tubes and trachea are sterile, because in the first place the bacteria 
entering with the air lodge on the mucous membrane of the 
nose and pharynx, where the current of air first strikes at an angle 
and sweeps over the moist surface, and in the second place be- 
cause they are carried up and out by the activity of the ciliated 
cells.) 

The act of coughing may itself be dangerous. In conditions 
which increase the irritability of the respiratory mucous mem- 
brane or of the pleura (inflammations) frequent coughing is ex- 
cited without there being anything requiring removal in the air 
passages. The violent expiratory "force of coughing raises the 
intra-pnlmonary air pressure and may thus cause pulmonary dis- 
tension (emphysema) ; it interferes with the return flow of venous 
blood into the thorax and heart, to the extent thai the latter 
may be practically empty, raises the arterial pressure all over 
the body, and may cause rupture of the vessels ( Krehl V The 



454 Urinary Disturbances. 

violent respiratory paroxysms by increasing the abdominal pres- 
sure may force the abdominal viscera into abnormally or normally 
existing openings and thus cause displacements [hernia] . 

Disturbances of the Urinary Excretion. 

The excretion from the blood of material no longer useful to 
the system through the kidneys, is subject to pathological faults 
if the quantity and quality of the blood passing through these 
organs are seriously changed, and if the renal parenchyma is the 
seat of pathological lesions. Increase in the quantity of the urine 
(polyuria), especially of the proportion of water in it, is met 
when the quantity of blood passing through the kidneys is greater 
than usual, that is, where arterial pressure is increased without 
any narrowing of the renal vessels, or where with the ordinary 
blood pressure the renal vessels are dilated. A more or less 
marked polyuria is met in a number of the acute and most of the 
chronic inflammations of the kidneys, and, too, after administra- 
tion of diuretic drugs, in connection with certain intoxications 
(mouldy oats, cantharides, colchicum, oil of turpentine), after 
resorption of transudates and exudates, in the stage of crisis in 
febrile infectious disease and in the conditions spoken of as dia- 
betes insipidus and diabetes mellitus. It may be readily under- 
stood that to a certain degree this phenomenon is due to chemical 
stimulation of the renal parenchyma with secondarily increased 
permeability of the dilated blood vessels, or to increased secretory 
action of the vascular endothlium and renal epithelium; on the 
other hand the causes of the increase of blood pressure, apart 
from increased ingestion of fluids, are as vet by no means clear. 
Cardiac hypertrophy, vaso-motor disturbances originating in the 
medulla, and paralysis of the renal nerves are worthy of consid- 
eration in this relation. The causative factors underlying the 
large output of urine occurring in so-called urinary flux or diabetes 
isipidus ( Sid/Scui/w, to pass through; insipidus, tasteless — in dis- 
tinction from diabetes mellitus) are equally obscure. 

Better information obtains in regard to the causes of diminu- 
tion of the quantity of urine (oliguria) and of total sunpression 
of urine (anuria). It must be obvious that all conditions in 
which the urinary passages are obstructed, as the urethra and 
ureters, by calculi, tumors, strictures, occlusion of the collecting 
tubules of the renal papillae by the shrinkage of the connective 
tissue about them or the retention of urinarv casts, plugs of 



Albuminuria. 455 

exudate, etc., must offer a resistance to the outflow of urine ; and 
any severe renal inflammations in which the epithelial cells be- 
come degenerated must reduce or stop entirely the secretory 
power of the organ. In the first group the tvrine is dammed 
back and pressure atrophy of the renal parenchyma takes place, 
the cortical portion continuing to secrete for a time and urine 
being unable to escape ; and in the other type of cases the pas- 
sages are open, but the original secretory disturbance determines 
a diminished production and a pathological composition of the 
urine. In case of unilateral disease such faults may be compen- 
sated by the opposite organ which remains functionally capable, 
which receives a larger proportion of the substance requiring ex- 
cretion in the urine, functionates more freely and becomes hyper- 
trophied. The secretion of urine must decrease also in conditions 
in which a diminished amount of blood flows into the kidnevs as 
the result of narrowing of their blood vessels, as from shrinkage 
of the renal capillaries and atrophy of the glomeruli fin chronic 
interstitial nephritis), from thrombosis of the renal arteries, or 
notably from lowering of blood pressure as in cardiac failure and 
a number of the above mentioned conditions. In the same way 
a reduction in the output of urine takes place when large quan- 
tities of fluid escape from the body by other routes or where the 
fluid is kept back in the tissues as in fevers, diarrhoeas, or forma- 
tion of fluid exudates and transudates in the body cavities. 

One of the most important pathological phenomena is the ex- 
cretion of albumen with the urine, albuminuria. In normal con- 
ditions, at least in states in which it is impossible to clearly dis- 
tinguish between normal and pathological conditions, it is true 
there is a very small quantity of the blood albumen passed 
through the kidneys, so small that it can only be recognized in 
Diirposefully concentrated urine and by special methods of de- 
termination, as after fatigue from physical exertion (so-called 
physiological and accidental albuminurias). When the amount 
n f albumen passed in the urine becomes sufficient to be recog- 
nized by the ordinary albumen reagents, there is reason to ap- 
prehend the pathological disturbance of the rennl function. This 
may be of a quickly transitorv nature, of no particular importance 
and indistinguishable from the above mentioned non-pathogenic 
symptomatic, conditions; but as a rule it is an indication of some 
lesion of the renal parenchyma. 

All sorts of poisonous substances, both those of external 



456 Urinary Disturbances. 

source (metallic salts, 'ethereal oils, etc.), and especially the tox- 
ines of infectious diseases and the products of intracorporeal 
tissue disintegration and metabolism, may give rise to lesions of 
the renal epithelial cells and their basement membranes, making 
it possible for the albumen of the blood to pass through them. 
In most cases an inflammation of the organ is also present, this 
factor introducing additional features of increased permeability 
of the blood vessels, exudation, desquamation of the epithelium 
and the formation of albuminous casts, blood casts, etc. -Some 
authors look upon every albuminuria as the result of an exuda- 
tive nephritis of some degree of severity, now unimportant, now- 
serious. 

* 
(For fuller details v. Friedberger-Frohner, Lehrbiich d. klin. Unter- 
suchungs method en. Verlag von F. Enke, Stuttgart, III. Aufl.) 

Another important symptom, often met in man, but uncom- 
mon in animals, is the excretion of sugar in the urine. Although 
the blood contains a considerable amount of sugar (as much as 
0.2 per cent.), only minute traces pass into the urine normally. 
In conditions in which unusual amounts of sugar are brought 
into the blood (alimentary hyperglycemia), and the liver and 
muscles are no longer able to use it up. the kidneys excrete the 
excess (glycosuria) ; milk sugar passes most readily and in order 
thereafter levulose, cane sugar and grape sugar (Krehl). It was 
discovered by Mering that the administration of the glucoside 
phloridzin, which contains about forty per cent, of sugar, is fol- 
lowed by a glycosuria in which not only does a considerable 
amount of the unchanged glucoside pass off in the urine, but also 
sugar from the blood (dextrose) and from the liver (glycogen), 
probably because of some secondary toxic lesion of the renal • 
epithelial cells. 

A transitory glycosuria, ending in the course of few hours, 
occurs after puncture of Claude Bernard's glycosuric point, a 
procedure consisting in making a fine puncture in a certain spot 
in the floor of the fourth ventricle of the brain. A similar glyco- 
suria may also be observed after lesions in other parts of the 
central nervous system and in a number of intoxications 'and in- 
fectious diseases (as in morphine poisoning, curare poisoning and 
rabies). If the splanchnic be cut at the same time, or the liver 
be extirpated, or if fasting animals are employed, the glycosuric 
puncture does not succeed or is uncertain, and therefore the 



Diabetes Mellitus. 457 

quantity of glycogen in the liver has something to do with the 
glycosuria; the precise character of the nervous influence is, how- 
ever, unknown. 

Where the excretion is a persistent and, too, a progressive 
symptom, provided no unusual quantities of sugar are ingested 
with the food, there may be said to exist a special disturbance of 
metabolism, diabetes mellitus (fuel, honey; diapaiva), , to pass 
through). In this affection even the ingestion of starch causes 
the appearance of grape sugar in the urine, so markedly, in fact, 
that the greatest portion of the starch instead of being assim- 
ilated passes off as sugar; and the urine only remains free from 
sugar if carbohydrates are entirely excluded from the food (Krehl 
and others). While in the milder cases of this disease the amount 
of proteid ingested has no influence upon the glycosuria, although 
the sugar is formed normally from proteid also, and while in 
these cases an increased supply of albuminous diet seems to be 
quite advantageous to the nutrition of the body, there are cases 
of a severe type in which even a strict meat diet and even absti- 
nence from all food dp not permit the urine to become free from 
sugar. Of what nature the metabolic disturbances may be which 
ar'e responsible for the imperfect manner in which the carbo- 
hydrates and the glycogen formed from proteid are dealt with is 
still rather obscure and confused (cf. Krehl). In a measure the 
liver normally prevents the direct passage of carbohydrates into 
the circulation and has the power of removing sugar from the 
portal blood and of storing glycogen. Diseases of the liver affect- 
ing this function permit a hyperglycemia to develop; (according 
to Bimes it ought to be possible to recognize the existence of 
hepatic disease by feeding molasses, as in case the liver were 
normal the urine would remain free from sugar while otherwise 
glucose would become demonstrable in it). Especial informa- 
tion has been obtained from the excellent investigations of Mering 
and Minkowski in relation to the pancreas, which have shown 
that diabetes mellitus occurs when this gland is lost (extirpation 
degeneration) and that either the pancreatic juice or the glandu- 
lar parenchyma, the blood from which passes to the liver by the 
portal vein, has in common with the liver a regulative influence 
upon the amount of sugar in the blood or some power of fixation 
of excesses of sugar (v. p. 448). [The generally favored view 
at present among the profession would refer the pancreatic fault 
to some disease of the islands of Langerhans (Opie). Tt is be- 



458 Urinary Disturbances. 

lieved that these special structures secrete and give into the blood 
of the pancreatic vein a substance which is either itself a glycolytic 
ferment or which is not a ferment, but a more simple substance 
acting to energize, a glycolytic ferment in the muscles and other 
tissues of the body. This glycolytic ferment is regarded as es- 
sential to the final transformations and chemical decomposition 
of the sugar in the system in order that it may be assimilated: 
in its absence assimilation is impossible and the body suffers 
by its inability to make use of the carbohydrates furnished to it, 
and at the same time the sugar in the blood accumulates and 
when in excess (above 0.4 per cent.) is excreted in the urine.] 

In its chronic form diabetes, an expression of metabolic fault 
and at times accompanied by faults of the liver and pancreas, 
causes more or less harm to the whole body. When the incom- 
plete assimilation of carbohydrates is not compensated by the 
supply of albuminates and fat, especially when the associated 
diseases do not permit the assimilation of these last named sub- 
stances, the general nutrition must of necessity fail. In serious 
cases there is apt to be present, as well, a marked proteid disin- 
tegration, and albuminuria appears as a symptom, together with 
degeneration of the lens and retina, disease of the blood vessel 
walls and a weakened resistive state of the tissues, which induces 
a. special predisposition to tuberculosis and gangrene (in man). 

Disturbances of micturition include difficult micturition 
(dysuria) caused by strictures and obstructions to the path of 
outflow (the dribbling forced passage, with tenesmus and frequent 
call to urinate, is called strangury) ; complete repression of mictu- 
rition {ischuria, retention of urine'), in which case the bladder is 
full because of spasm of the sphincter or paralysis of the detrusor 
musculature; and inability to retain the urine (enuresis, incon- 
tinentia urince), due to a paralysis of the sphincter of the bladder 
developing in disease of the spinal cord and of the bladder itself. 

(For details cf. Friedberger-Frohner, Klinischc Untersuchungsmetho- 
dcn.) 

Diseases of the urinary apparatus are more or less painful ; 
affections of the passages being particularly apt to cause intense 
pains, to be attributed in part to muscle spasms, partly to me- 
chanical irritation (foreign bodies) of the sensory filaments of 
the mucous membrane or to specially induced irritability (ulcers, 
abrasions, inflammations) of these filaments. 



Uraemia; Thyroid Disturbances. 459 

The effect of disturbances of the uropoietic system upon the 
general body depends upon the extent and the kind of the 
changes. All the bacterial processes in the kidneys and in the 
collecting" receptacles (bladder, renal pelves) as well as the 
damming back of the urine in the ureters bilaterally, sooner or 
later bring about symptoms of intoxication, manifesting them- 
selves especially by symptoms of cerebral depression, less fre- 
quently cerebral excitation, included collectively under the 
term urcemia. This is partly referable to the impaired excretion 
from the blood of substances no longer of use in the economy 
and having toxic influences when retained, as the products of 
proteid decomposition particularly; and the kidney is itself a place 
in which special metabolic processes are carried on, the products 
of which, as hippuric acid (Bunge and Schmiedeberg), if retained 
may apparently take part in the production of uraemia. The 
regulation of the proportion of water in the blood is apt to be 
disturbed in chronic renal affections ; and, too, because of shrink- 
age of the comparatively large capillary area of the kidneys, a 
certain amount of resistance is likely to develop to the arterial 
blood flow ; in these chronic affections, therefore, hydraemia, cardiac 
hypertrophy and general dropsy may be expected as secondary 
features. 

Disturbances of the Thyroid Function. 

Destruction of the thyroid tissue by atrophy, degenerative 
processes or heterologous tumors, involves the loss of an organic 
function of vital importance ; disturbances of nutrition, loss of 
physical strength and spasmodic attacks being induced, indicative 
of a general autointoxication of the body and leading to a fatal 
termination. In case of total extirpation of the thyroid gland 
[including the parathyroids] intense nervous symptoms (delirium, 
tetanic convulsions, and so-called tetany) quickly appear, as ob- 
served in man. Dogs usually die after such operations in from 
three to twenty-eight days and, too, under circumstances where 
injury to nerves, etc., cannot be held responsible. After removal 
of large portions of the thyroid there is also danger of autointoxi- 
cation. Where the symptoms develop slowly, as is particularly 
true in pathological atrophy of the glandular tissue, the resultant 
condition is spoken of as cachexia strumipriva or athyrea; and 
besides the nervous symptoms there may be observed spasmodic 



460 Athyrea; Hyperthyrea. 

dyspnoea, disturbances of growth, dilution of the blood and 
cutaneous changes (falling out of hair, thickening and mucoid 
degeneration of the subcutaneous tissue — myxedema atrophicum, 
strumosum, operativum) . Practically the same results are ob- 
tained from experiments on monkeys, sheep, goats, hogs and dogs 
as are observed in man after goitre operations (Hofmeister and 
Eiselberg) . 

[The acute results mentioned, tetany, dyspnoea, convulsions, 
palsies and death in a few days after ablation, are now generally 
attributed to loss of the parathyroid glandules ; removal of the 
thyroid alone is not essentially fatal, and is followed by chronic 
metabolic disturbances in animals comparable to myxcedema in 
man. The precise interrelation which probably exists between the 
thyroid and parathyroids is not understood.] 

It has been assumed (Rogowitsch) that the thyroid gland has 
as its function the removal or neutralization of metabolic products 
the retention of which in the system would produce toxic effects, 
that the organ probably, therefore, elaborates a secretory sub- 
stance essential to the regulation of metabolism, which is appar- 
ently carried into the blood from the follicles by way of the ex- 
tremely delicate lymph channels (Lubarsch). This assumption is 
founded upon the fact that a fatal result of operative removal 
may be avoided by removing only one lobe of the gland and by 
leaving some remnant of thyroid tissue or by favoring restoration 
of the tissue by artificial means (transplantation of thyroid, in- 
jection of thyroid extract), or if the parathyroids remain and take 
up a vicarious [ ?] activity. It seems probable that the hypophysis 
is able in some degree to compensate for loss of the thyroid by 
vicarious hypertrophy; at least in thyroidcctomized rabbits en- 
largements of the pituitary body have been observed (Rogo- 
witsch, Stieda, Hofmeister). 

In connection with enlargements of the thyroid {struma hyper- 
plastica and, too, cavernosa) a type of intoxication has been ob- 
served, apparently the very opposite to that following extirpa- 
tion of the organ, the so-called Basedow's disease {hyperthyrea, 
dysthyrea) ; this condition is very like the symptoms of intoxica- 
tion which occur both in healthy human beings and animals 
after large doses of thyroid extract, as accelerated and energetic 
cardiac action (tachycardia), cardiac dilatation and cardiac hyper- 
trophy, epileptiform seizures, prominence of the eyeballs (goggle- 



Sexual Disturbances. 461 

eyes, exophthalmus), and various results of these disturbances. 
The condition apparently depends, as pointed out by Mobius, 
Greenfield, Rehn and others, upon a functional disturbance of the 
organ which occasions either a quantitative, or qualitative change 
in the secretion (an excess of the secretion or one in which there 
is a chemical change) ; but there are numerous uncertainties in 
relation to these points, as for example, the failure of a case of 
Basedow's disease to recover after extirpation or atrophy of the 
gland (Lubarsch). Jewsejenko claims to have met this last dis- 
ease also in animals (dog, horse) ; Reynard and Rongieux have 
observed stupidity in dogs and horses after development of goitre. 

Cretinism and chondrodystrophy have been regarded as dependent upon 
the thyroid function, but according to Lubarsch's studies there is appar- 
ently no. setiological relationship. 

Disturbances of the Sexual Function. 

Diseases and congenital anomalies of the sexual glands render 
the individual impotent to produce viable offspring, in males pre- 
venting * formation of semen or procreation (impotence, impo- 
tentia generandi et coeundi), in female animals interfering with 
ovulation, fertilization of the ovum and maturation of the embryo 
(barrenness, sterility). Even general diseases (as fever, various 
painful affections of the muscles and joints, diseases of the spinal 
cord) may indirectly influence the sexual function (loss of ex- 
citability, mechanical interferences). According to Zschokke 
even if only one ovary is diseased there is, as a rule, a disturb- 
ance of the general sexual vitality. A number of affections of 
the sexual glands, as tuberculosis of the ovaries, chronic inflam- 
mation or cystic changes of these organs, or undescended testicle, 
are apt to be accompanied by special excitability of the sexual 
appetite (constant rutting, bulling, horsing, nymphomania, saty- 
riasis), sometimes with violence of temper. In other cases, how- 
ever, destruction of the sexual glands by disease or removal b> 
castration is followed by suppression of sexual vitality, altera- 
tions in the state of nutrition, and changes in the bodily struc- 
ture (change in the type of horns in oxen, loss of antlers in stag 
and roe-deer, shape of body approximating female type, fat ac- 
cumulation, gentle disposition in castrated male animals). 

(For details cf. Zschokke, ,I)ir Unfruchtbarkcit des Rindcs, Zurich, 
1900.) 



462 Disturbances of Cutaneous Function. 

Local abnormalities of the uterus mav, in a mechanical wav, 
determine the development of embryonal monstrosities or the 
death and premature expulsion of the foetus {miscarriage, abor- 
tion). 

In cows and goats, less frequently in hogs, a form of paralysis 
not infrequently appears within the first few days after parturi- 
tion, at the time of establishment of lactation, the so-called 
paralytic calf-fever or paralysis of parturition. The cause of the 
condition, as Schmidt (Kolc[ing) has pointed out, depends on an 
autointoxication related with the formation of colostrum. The 
colostrum milk is very rich in disintegrating epithelium of the 
mammary gland and apparently contains decomposition products 
from these elements, which, if absorbed in large amounts, are 
capable of giving rise to toxic effects. The condition is met espe- 
cially in animals producing large amounts of milk, in case of un- 
usually marked colostrum formation. The excellent results of 
therapeutic measures directed to reduce the milk secretion and 
causing oxidation of the poisonous products by introducing oxy- 
gen into the udder and thus rendering them inert, permit the 
acceptance of Schmidt's theory as well founded. 

Disturbances of the Cutaneous Function. 

The skin, with its epidermal covering, is an organ of defense 
to the body against the harmful influences of the exterior. Any 
traumatic denudation of the papillary layer or deeper wound de- 
stroys the protection it affords, and not only exposes the denuded 
surface to the drying influences of the air, but serves as a focus of 
entrance of infectious agents as well, since the injury opens easy 
access into the lymphatic paths. Long continued soaking of the 
epiderm causes its maceration (by nasal discharge, urine, etc.). 
continuous pressure leads to callosites or by contusion at places 
which overlie bony prominences to ruptures of vessels, haemor- 
rhages, and in this way to disturbances of nutrition which may 
cause necrosis of the skin (decubitus, decubital gangrene). The 
loss of albuminates occasioned by leakage of lymph in case of 
denudation of the epiderm (running sores of the skin and mouth) 
may cause material deterioration of the state of nutrition of the 
body (Landois). 

To what extent disturbances may be caused by suppression 
of the cutaneous interchange of gases (output of water and car- 



Disturbances of Perspiration. 463 

bonic acid gas in the perspiration) we have but little knowledge. 
According to Ellenberger in horses, which were shaved and then 
covered with a coat of varnish, there appeared slowing of respira- 
tion, acceleration of pulse, a fall of the body temperature of one 
to one and a half degrees centigrade, symptoms of uneasiness, 
muscular twitchings, polyuria and increased excretions of urea, 
these symptoms soon disappearing; the animals took their food 
without being at all urged and at the end of the experiment 
showed a greater body weight than at the start. Hogs and dogs, 
after being varnished, showed no disturbances of health beyond a 
depression of the body temperature (cited from Schindelka). 
Sheep, however, after being coated with varnish, apparently suffer 
considerably (Ellenberger), and rabbits die if no more than one- 
eighth of their body surface be covered with varnish, apparently 
because of excessive heat dissipation (Landois, Fourcault, Bec- 
querel and Brechet) ; in case the whole surface of the body is 
varnished the temperature at once drops (to 19 C). 

For consideration of chilling of the skin, cf. p. 45. 

Because of the vast numbers of sensory nerves ending in the 
skin the least denudation of the papillary layer and inflammatory 
swelling of the cutis, as well as contact with foreign bodies, oc- 
casion marked sensations of pain. 

Pathological increase of perspiration, hyperidrosis (idpdw, to 
sweat), may be met in a great variety of conditions which give 
rise to an excited state of the perspiratory centres in the medulla 
oblongata and cord (excess of carbon dioxide in the blood, de- 
ficiency of oxygen, sensory and psychic stimulation). Sweating 
may be general or local, sometimes unilateral, or limited by a trans- 
verse border strictly to the posterior portion of the body. In 
these latter examples disturbances in the nervous distribution are 
usually at the bottom of the trouble ; the abnormality is especially 
striking in dogs which do not sweat normally. 

Diminished secretion from the glands allied to sweat glands, 
which are met in the muzzles of the ruminants, the snout in pigs 
and nose in dogs, as a result of which these parts, otherwise 
always moist, come to feel dry, is a marked symptom in all febrile 
diseases. 

In case of the entrance of urine into the peritoneal cavity 
after rupture of the bladder, or in urinary infiltration of the cellu- 
lar tissue after rupture of the urethra, the perspiration may take 



464 Disturbances of Cutaneous Function. 

on a urine-like odor; and in distemper in dogs and in the pock of 
sheep the skin gives off an unpleasant, offensive odor. 

A rough, bristling appearance of the hair, brittle, dry wool, 
is a symptom of chronic nutritive faults; the same may be said 
of diminution of the subcutaneous fat, when it becames tight, in- 
elastic and adherent to the underlying fasciae (so-called hide- 
binding of the skin). 

(For details v. Friedberger-Frohner, Lehrbuch d. klinisch. Untersuch- 
ungsmethoden f. Tierarzte, Verl. von Ferd. Enke, Stuttgart, III. Auil.) 



Plate I 




Fig. 1. Acute fibrinous pleurisy of horse. Yellow fibrinous exudate spread 
over the reddened, somewhat clouded, pleura of the right lung. 




lung. 



Fig. 2. Chronic cheesy tuberculous pneumonia. Section of lobe of cow's 



Plate II. 




Fig. 1. Gangrene of skin of lower jaw of hog. 




Fig. 2. Hyperemia of skin in swine erysipelas. 



Botf III. 




Fig. 1. Section of scrotum of bull with cheesy coagulation necrosis of tes- 
ticle; the scrotal sac was filled with a sero-purulent exudate; the tunica vaginalis 
communis and subcutaneous tissue were surrounded by a dense abscess capsule; 
and a large blood clot was seen distributed throughout the sac. 




Fig. 2. Focalized necrosis of liver of cow; the section shows the nodules of 
coagulation necrosis of natural size. 



Plate IV 



1. 




Fig. 1. Acute croupous enteritis; a portion of cow's intestine laid open; 
the mucous membrane is the seat of hyperaemia and false membrane formation. 



2. 




X 



Fig. 2. Fatty liver of hog. 



INDEX 



A PAGE 

Actinomycosis 3 I 8 

Fungous Growths of 320 

Fungus of 1 . 321 

Actinomycotic Abscesses 320 

" Nodules 3 2 o 

Active Hyperemia 112 

" Immunization 28 

Acute Diseases 95 

Adenocarcinoma 39 1 ? 4°7 

Adenocystoma * 418 

Adenofibroma Pericaniliculare . . 390 

Adenoma 388 

^Etiology of 391 

Varieties of 389 

Adenosarcorna 391 

Agglutinins 26 

Air Embolism 149 

" Hunger 449 

Akinesis 429 

Albuminous Degeneration ....'.. 190 

Albuminuria 455 

Alexins 19 

Algor Mortis 104 

Alimentation, Disturbances of... 36 

Amaurosis 433 

Amblyopia 433 

Amboceptor , 25 

Amputation Neuroma 250, 358 

Amyloid Degeneration . 205 

" of Liver . . . 207 
" " Spleen .. 208 

Reaction 206 

Anaemia 118, 157 

Anaemic Infarct 145 

Anaesthesia 432 

Anamnesis 93 

Anasarca 130 

Anatomical-pathological Proces- 
ses 3 

Anatomical Types of Inflamma- 
tion and Exudate 272 

Angioneurosis 435 

Angioplasts 240 

Animal Parasites j6 

Poisons 51 

Ante-mortem Clots 132 

Anthracosis 215 

Antibodies .. . .' 22 



PAGE 

iAntitoxine 24 

Anuria 454 

Apoplexy 425 

Apparent Death 105 

Argyria 215 

Aristotole 11 

Ascites 130, 447 

Asphyxia 38, 451 

as Cause of Death.... 39 

Ataxia \ . . 429 

Athyrea 459 

Atony of Stomach 439 

Atrophy 185 

Causes of 186 

Autoblastomata 325 

Autochthonous Melanosis 209 

Thrombi 136 

B 

Bacillus Mallei 311 

Bacteria 54 

Mode of Invasion of . . 61 

Specific Action of 67 

Bacteriaemia 66 

Basedow's Disease 460 

Bile, Abnormal Secretion of.... 446 

Biliary Stasis 212, 446 

Blood Corpuscles, Regeneration 

of 251 

Blood, Impoverishment of 157 

Pathological Changes of. 156 

" Variations in in 

Vessels, Regeneration of. 240 

Bone, Regeneration of 246 

Botryomycosis 324 

Fungus of ...... 324 

Brain, Compression of 425 

( " Symptoms of 425 

" Stroke 425 

Buffy Coat [3] 

Burns [2 

Fatality of 43 

C 

Cachectic (Edema [28 

Cachexia [90 

of Cancer n.j 

Strumipriva 450 






4 66 



Index. 



PAGE 

Cadaveric Clots 132 

Calcification 216 

Calculi 216, 219 

Biliary 223 

Intestinal 226 

Required Conditions of. 219 

Salivary 225 

Urinary 220 

Callus 247 

Cancer 394 

Cachexia of 414 

Cellular Morphology of. 402 

Colloid 412 

Cylindrical Cell 406 

Dissemination of 400 

Glandular Cell 406 

Gross Appearance of . . . 410 

Metastasis of 401 

Origin of 396 

Pearls 405 

Scirrhus 413 

Transplantation of 398 

Varieties of 403 

Carcinoma 394 

Cardiac Hypertrophy 106 

Insufficiency 100 

Cardinal Symptoms 260 

Cartilage, Regeneration of 246 

Caseation 179 

Catalepsy 428 

Catarrhal Exudate 273 

Catching Cold 45 

Causes of Disease 35 

Cavernous Hemangioma ...362, 363 

Cellular "Pathology 14 

Cerebro-spinal Concussion 424 

Cheesy Tuberculous Infiltration. 306 

Chemical Agents 50 

Chemico-pathological Processes. 4 

Chemotaxis 18, 161 

Chilblain 45 

Cholsemia 447 

Cholelithiasis 223 

Cholesteatoma 382 

Cholesterin 195 

Chondroma 350 

Chronic Diseases 95 

Chronic Inflammation 284 

Circulation, Disturbances of.... 106 

Circulation, Schema of 140 

Classification of Inflammatory 

Processes 288 

Clinical Observation 

Clonic Spasms 428 

Clot, Absorption of 125 

" Formation 131 

Cloudy Swelling 190 

Coagulation Necrosis 179 

Coagulins 26 

Cohnheim's Theory 336 



PAGE 

Colic 444 

Collateral Circulation 143 

CEdema 128 

Colloid Degeneration 204 

Substances 204 

Coma 425 

Commotio Cerebri 424 

Comparative Pathology 14 

Compensation for Circulatory 

Abnormalities 106 

Compensatory Hypertrophy .... 255 

Complements 19, 25 

Complications 99 

Concretions 216, 219 

Concussion 50, 424 

Congenital Diseases 30 

Connective Tissue, Regeneration 

of •_ 237 

Consciousness, Loss of 424 

Consecutive Thrombi 136 

Constipation 443 

Constitutional Predisposition ... 31 

Contagious Diseases 71 

Continued Fever 173 

Convalescence 173 

Convulsions 428 

'Corpora Amylacea 208 

Flava 208 

Versicolorata 208 

Corrosive Poisons 52 

Cough 452 

Cramp 428 

Croupous Exudate 275 

Inflammation 275 

Cruor Sanguinis 131 

Cylindrical Cell Cancer 406 

Cylindroma 382 

Cystic Tumors 415 

Cystoma Penniferum 417 

Cytolysins 25 

D 

Death 101 

Agony 103 

Causes of 102 

" Local 176 

Signs of 104 

Decubitus 462 

Degenerative Processes — 

Albuminous 190 

Amyloid 205 

Colloid 204 

Fatty 192 

Hyaline 199 

Mucoid 202 

Delirium 426 

Demarcating Inflammation . .184, 269 . 

Depression of the Brain 425 

Dermoid Cysts 416 



Index. 



467 



PAGE 

Diabetes Insipidus 454 

" Mellitus 448, 457 

Diagnosis 91, 93 

Diapedesis 120 

Diarrhoea 442 

Digestive Disturbances 436 

Dilatation of the Heart 109 

Diphtheritic Inflammation 276 

Direct Symptoms .■ 92 

Disease 1 

Causes of 35 

Conception of 2 

Course of 91, 94 

" Periods of 96 

Recovery from . 100 

Symptoms of 91, 99 

Termination of 99 

Diseases, Congenital and Inher- 
ited 30 

Diseases of First Stomach 439 

" Intestines 440 

"Jaw 436 

" Liver 444 

" Month 436 

" (Esophagus 437 

" Pancreas 447 

" " Pharynx 437 

" Stomach 437 

" Teeth \ . . 436 

Dissemination of Germs in the 

Body 65 

Disturbances of Alimentation 

and Nutrition 36 

Disturbances of Circulation 106 

Disturbances of Excretion of 

Urine 454 

Disturbances of Function of Skin 462 
Disturbances of Metabolism .... 165 
Disturbances of Respiration .... 448 
Disturbances of Sexual Func- 
tion 461 

Disturbances of Thyroid Func- 
tion 459 

Dizziness 424 

Dropsical Transudate 129 

Dropsy ' 126 

Dwarfism 31 

Dyspepsia 438 

Acida 438 

Dysperistalsis 443 

Dyspnoea • , . 449 

Dysuria 458 

E 

Ecchondroma 351 

Ecchymoses 122 

Ectogcnous and Entogenous In- 
fectious Agents 70, 71 

Ehrlich's Theory 22 

Electrical [nfluences 48 



PAGE 

Emboli 131, 138, 149 

" Course of 139 

Embryoma 421 

Emphysema 450, 453 

Empyema 281 

Enchondroma 351 

Endarteries 144 

Endemic Disease 72 

Endothelioma 380 

Endotoxines 58 

Enostoses 354 

Enteroliths 227 

Enuresis 458 

*Eosinophilia 163 

Ephemeral Fever 173 

Epidemic Disease 73 

Epiderm and Epithelium, Re- 
generation of 242 

Epilepsy 425, 428 

Epithelial Cysts 415 

Exhaustion 40 

Exitus Lethalis 101 

Exogenous Pigmentation 215 

Exostoses 354 

Expectoration 453 

'Experimental Pathology 8 

External Respiration 448 

Exudate 264 

Eye in Death 105 

F 

Fainting 424 

Falling Sickness 425 

False Membrane 274 

Fat Embolism 150 

Fatty Changes 192 

''' Degeneration 193, 198 

" Infiltration 192 

Faults of Heat Regulation 165 

Fecal Concretions 226 

Fever 165 

Production of 168 

Stages of 171 

Types of 170 

Fibrino-purulent Exudate 278 

Fibrinous Exudate 27s 

Fibroblasts 237 

Fibroma 341 

Durum 341 

Growth of 345 

Molle 342 

Fibromatosis 345 

Fistula 282 

Flatulence 139 

Food, Deprivation of 36 

Freezing 44 

Functional Abnormalities 423 

Overstimulation .... 40 
Pathological Disturb- 
ances 4 



4 68 



Index. 



G PAGE 

Galen 12 

Gall Stones 223 

Composition of .... 223 

Gangrene 181 

Gangrenous Emphysema 183 

Gastric Atony 439 

Gelatinous Cancer 412 

General Nervous Disturbances.. 423 

Pathology .■ 5 

Germinal Variation 32 

Giant Cells 239 

Cell Sarcoma 368 

Gigantism 31, 254* 

Glanders 311 

Abscesses 315 

Bacillus of 311 

Indurations 315 

Nodules 314 

Ulcers 314 

Glands, Regeneration of 244 

Glandular Cell Cancers 406 

Glioma 360 

" Retinal 361 

Glycogenic Infiltration 205 

Glycosuria 456 

Gout 229 

Granulation Tissue ....241, 283, 285 

H 

Hemangioma 362 

Hematemesis . . . 122 

Hematocele 122 

Hematogenous Pigmentation . .. 210 

Hematoma 122 

Hematuria 122 

Hemic Poisons 53 

Hemochromatosis 210 

Hemoglobinemia 160, 210 

Hemoglobinuria 160, 211 

Hemolysins 25 

Hemopericardium 122 

Hemoptysis 122 

Hemorrhage 119 

Results of 124 

Symptoms of 122 

Varieties of 121 

Hemorrhagic Anemia 158 

Infarct 145 

Inflammation .... 283 

Hemosiderin 211 

Hemothorax ._ 122 

Haptophore 23 

Health, Definition of 1 

Heart, Condition of, in Disease. 106 

Heat Regulation, Faults of 165 

" Stroke 41 

Hemiplegia 429 

Hereditary Defects of Animals. . 34 

" " Man .... 33 



PAGE 

Hereditv, Atavistic 33 

Collateral 33 

Direct 33 

Latent 33 

Heterotopic, Heterochronic and 

Heterometric Processes 3 

Hippocrates 11 

History of Pathology 10 

Hodgkin's Disease 373 

Homogeneous Thrombi 134 

Hoof, Regeneration of 243 

Host of a Parasite 77 

Humoral Pathology 11 

Hyalin Degeneration 199 

Hydremia 161 

Hydrocele 130 

Hydrocephalus 130 

Hydropericardium 130 

Hydrops 126 

Hydrothorax 130 

Hyperacidity 438 

Hyperemia 112 

Hyperesthesia 431 

Hypercholia 213 

Hyperchromatosis 209 

Hyperglycemia 456 

Hyperidrosis 463 

Hyperkinesis 427 

Hyperleucocytosis 162 

Hypernephroma 393, 397 

Hyperthermia 41, 165 

Passive 166 

Hypertrophy 254 

I 

Icterus 212, 446 

Idiosyncrasy 20 

Ileus 444 

Immunity 16 

Acquired 21 

" Active 28 

Natural 24 

Passive 28 

" Relative 20 

Impotence 461 

Incubation, Period of 64 

Indirect Symptoms 92 

Infarction 145 

Infection 54 

Embolic 65 

General 66 

Local 65 

Regional 65 

Infectious Agencies 54 

Diseases and Their- 

Agents, Table of . . 73 

Matter 55 

Inflammation 258 

Anatomical Types of 272 

Cardiac Valves .... 272 



Index. 



469 



PAGE 

Inflammation, Cardinal Symptoms 

of 260 

" Causes of 258 

Chronic 284 

Corneal 271 

Interstitial 285 

Nomenclature and 

Classification .... 288 

Phenomena of .... 260 

" Productive 284 

Specific 286 

Suppurative 277 

Termination of .... 289 

Inflammatory (Edema 128, 273 

Inherited Diseases 30 

Insanity 426 

Intermittent Disease 95 

Intestinal Calculi 226 

Intestines, Diseases of. 440 

Fermentation in .... 441 

Intoxication 50 

Intrauterine Disease, Origin of. . 31 

Intussusception . 443 

Irritability, Psychic 426 

Ischsemia 118 

Itching 432 

J 

Jaundice 212 

Sequels to. ... .' 214 

L 

Latent Disease 97 

Leiomyoma 357 

Leucocytosis 162 

Leucopenia 162 

Leukaemia 163 

"Licking" 427 

Lightning Stroke 48 

Lipoma 346 

Occurrence of 348 

Liquefaction Necrosis 181 

Liver, Diseases of 444 

Functions of 445 

Local Variations in Amount of 

Blood in 

Low Temperatures, Effects of. . 43 

Lungs, Diseases of 448 

Lymphangioma 364 

Lymphatic Thrombosis 154 

Lymphatismus 372 

Lymphogenous Embolism 154 

Lymphoma 372 

M 

Malignant Embolism 151 

Mania 426 



PAGE 

Marasmus 190 

Mechanical Influences 49 

Melanin •. . 209 

Melanoma .' 377 

Melanosarcoma 377 

Melanosis 209 

Metabolism in Fever 173 

Metastasis 151 

Meteorism 439 

Methsemoglobin 160 

Metrorrhagia 122 

Miasmatic Disease 71 

Microbes 54 

Microphytes 17 

Microzoa 17 

Miliary Tubercle 300, 303 

Mineral Poisons 51 

Miscarriage ^62 

Miserere 444 

Mixed Infection 69 

Thrombi 135 

Motor Disturbances 427 

Automatic . 427 

Coordinated 427 

Reflex 427 

Voluntary . 427 

Mucoid Degeneration 202 

Mummification 179 

Muscle, Regeneration of 245 

Myelogenous Sarcoma 369 

Myoma 356 

Myositis Ossificans Progressiva. 355 

Myxcedema 460 

Myxoma 349 

Myxosarcoma 369 

N 

Necrosis 176 

Causes of 177 

Symptoms of 183 

Terminations of 184 

with Coagulation 179 

Desiccation .... 179 

Putrefaction ... 181 

Softening 181 

Neoplasms 325 

Nerves, Regeneration of . 248 

Nervous Disturbances 423 

Hypertrophy 257 

Neuralgia 431 

Neurofibroma 330 

Neuroma 35S 

Amputation 250, 358 

Neuromyxoma 351) 

New Growths 325 

Nosology 5 

Nutrition, Disturbances of 36 

Nymphomania 426 



470 



Index. 



O page 

Obesity 197 

Obstruction of Intestines 443 

" Blood Vessels... 131 

Occluding Thrombi 136 

Odontoblastoma 418 

Odontoma 418 

Durum 419 

JMixtum 419 

GEdema 126 

Results of 130 

Oligemia 157 

Oligocythemia 157 

Oliguria 454 

Oncology 326 

Organization of Thrombi 138 

Osteoclasts 248 

Osteocystoma 420 

Osteoma 353 

Varieties of 353 

Osteo-sarcoma 353 

Oxygen Supply, Deprivation of.. 38 

P 

Pain 431 

Palsy 429 

Results of 430 

Pancreas, Diseases of 447 

Pandemic Disease 72> 

Papilloma 383 

Paradoxical Embolism 142 

Paresthesia 432 

Paralysis 429 

Paralytic Calf Fever 462 

Paraplegia 429 

Parasites 76 

Table of 82 

Parasitic Diseases 76 

Parenchymatous Inflammation. . 287 

Poisons 53 

Passive Congestion 115, 127 

Hyperemia 114 

Hyperthermia 166 

Pathogenesis 4 

Pathogenic Microorganisms .... 55 

Pathognomonic Symptoms 92 

Pathognomy 5 

Pathological Changes of the 

Blood 156 

Pathological Processes, Classes 

of 3 

Pathology 1 

History of 10 

Periostoses 354 

Perithelioma 382 

Petechiae 122 

Petrification 216 

Phagocytosis 18, 161 

Pharynx, Diseases of 437 

Phlegmon 282 

Pigmentation 209 

Pigmented Tumor 377 



PAGE 

Placental Origin of Disease 30 

Plethora 157 

Poikilocytosis 159 

Poisons 50 

Classification of 52 

Polychromatophilia 159 

Polymorphocellular Sarcoma.... 369 

Polyuria 454 

Post-mortem Clots 132 

Precipitins 26 

Predisposition 16 

Pressure Atrophy 187 

Primary Lesion 98 

Thrombi 136 

Processes of Repair and New 

Formation 232 

Productive Inflammation 284 

Prognosis 94 

Progressive Inflammatory Ostei- 

tosis 355 

Prophylaxis 5 

Protective Substances 21 

Proud Flesh 286 

Psammoma 382 

Psychical Disturbances 424 

Excitement 426 

Ptyalism 436 

Pus 277 

Concretions 228 

Putrefaction After Death 105 

of Exudate 283 

Putrid Necrosis 181 

R 

Ray Fungus 321 

Receptor 22 

Recovery from Disease 100 

Red Thrombi 135 

Regeneration 232 

Capacity for 235 

" of Blood and Lymph 251 
" Blood Vessels ... 240 
" Bone and Car- 
tilage 246 

" Connective Tissue 237 
" Corneal Epithe- 
lium 243 

" Epiderm and Epi- 
thelium 242 

" Glands 244 

" Hair 243 

" " Horny Tissue... 243 

" Muscle 245 

" " Nerves 248 

" " Tendon Tissue.. 246 

Remittent Disease 95 

Resistance to Disease 16 

Respiration, Disturbances of.... 448 

Respiratory Faults 38 

Retrograde Embolism 142 

Rhabdomyoma 356 



Index, 



471 



PAGE 

Riding Embolus 139 

Rigor Mortis 104 

Round Cell Sarcoma 367 

S 

Sago Spleen 208 

Salivary Calculi 225 

Salivation 436 

Sapremia 185 

Saprophytes 56 

Sarcoma 365 

Cells of 365 

Classes of 366 

Development and ^Eti- 
ology of 37i 

Gross Appearances of. 370 

Scars Following Infarction 147 

Scirrhus Cancers 413 

Secondary Lesions 98 

Thrombi < 136 

Secretory Abnormalities 435 

Sensation, Pathological Diminu- 
tion of 432 

Sensory Disturbances 431 

Sequestration 178, 184 

Sero-fibrinous Exudate 275 

^Serous Inflammation 273 

Exudate 273 

Sexual Organs, Diseases of.... 461 

Shock 50 

Side-chains 22 

Skin Diseases 462 

Spasms 427 

Results of 429 

Special Pathology 5 

Spindle Cell Sarcoma 368 

Squamous Epithelioma 404 

Starvation 36 

Stellate Cell Sarcoma 369 

Sterility 461 

Stomach, Diseases of 437 

Strangulation of Intestine 443 

Stratified Thrombi T35 

Struma Petrificans 219 

Sudden Death 103 

Suffocation , 451 

Suffusion of Blood 122 

Suppuration 277 

Symptomatology 91 

Symptoms of Death 104 

Syncope 424 

T 
Tendon Tissue, Regeneration of. 246 

Teratoma 415, 421 

Terminations of Disease 99 

Therapeutics 94 

Therapy 5 

Thermic Influences 41 

Thermometry 175 

Thrombosis 131 



PAGE 

Thrombosis, Causes of 132 

Results of 142 

Thyroid Function, Disturbances 

of 459 

Tissue Immunity 63 

Predisposition 63 

Tonic Spasms 428 

Toxalbumens 5 1 

Toxines 51, 57 

Toxophore 23 

Transplantation 251 

Traumatic Influences 49 

Trophic Disturbances 434 

Tuberculin 310 

Tuberculosis 291 

Anatomical Lesions 

of 298 

Bacillus of 292 

Heredity of 295 

Mode of Contagion. 294 

Symptoms of 310 

Tuberculous Cavities 307 

Granuloma 305 

Ulcers 305 

Tumors 325 

Etiology of 333 

" Cohnheim's 

Theory .. 336 

Classification of 340 

External Shape of 328 

Growth of 328 

Pathological Significance 

of 329 

U 

Ubiquitous Disease 72 

Ulcer 282 

Undernutrition 38 

Uniceptors . 24 

U Hernia 459 

Urinary Calculi 220 

Gravel 220 

Organs, Diseases of.... 454 

Urolithiasis 220 

V 

Valvular Thrombi 136 

Vasomotor Disturbances 435 

Vegetable Poisons 51 

Vertigo 424 

Vibiccs 122 

Virulence of Toxines 58, -59 

Vomiting 440 

Vomitus 440 

W 

Wart 385 

Water, Withdrawal of 37 

White Thrombi 135 

Work Hypertrophy 254 



W. T. KEENER & COMPANY 

Medical Publishers and Importers 
90 WABASH AVENUE, - - CHICAGO 

TEXT-BOOK OF COMPARATIVE GENERAL PATHOL- 
OGY FOR THE USE OF PRACTITIONERS AND 
STUDENTS OF VETERINARY MEDICINE. 

By PROF. DR. TH. KITT, of Munich. 

Authorized translation from the German by Dr. William W. Cadbury, 

Assistant Demonstrator of Pathology ; Edited by Dr. Allen J. Smith, 

Professor of Pathology in the University of Pennsylvania. 

One volume, royal 8vo. With four colored plates and one hundred and 
thirty-one illustrations in the text. Cloth, $5.25 net. 



Kitt's work on General Pathology is the only especial text- 
book on Veterinary Pathology published. Heretofore students 
and veterinary surgeons have had to consult works on human 
medicine in order to learn the foundations of pathology ; this vol- 
ume, however, is written#with special reference to the student of 
animal medicine. 

After an introductory review of the general conceptions of 
disease and of the history of pathology, the causes of disease are 
discussed ; then pathologic disturbances' under four main headings, 
viz.: (1) Circulatory Disorders; (2) Metabolic Disorders, Degen- 
erations and Necroses; (3) Reparatory Processes and Prolifera- 
tion ; (4) Functional Disorders. All of the most common and 
characteristic processes are illustrated by a number of original 
drawings and colored plates. 

The style of the book is terse and concise and all the defini- 
tions are clear cut ; the work is thoroughly up to date, as all the 
results of the recent investigations with the pathology and etiology 
of disease are included in the text and are described in a very 
simple and popular manner. The practicing veterinarian will find 
in this book a modern work, convenient for ready reference, and 
containing everything that we know to-day regarding Veterinary 
Pathology. 

W. T. Keener & Co., Chicago. 



SURGICAL DISEASES OF THE DOG AND CAT. 

With Chapters on Anaesthetics and Obstetrics. 

(Second Edition of Canine and Feline Surgery.) 

By FREDERICK T. G. HOBDAY, F. R. C V. S., F. R. S. E. 

Member of the Board of Examiners of the Royal College of Veterinary 
Surgeons ; Late Professor in the Royal Veterinary College, London ; 
Consulting Veterinary Surgeon to the British Bulldog and Griffon 
Bruxellois Clubs ; Honorary Veterinary Surgeon to the Ladies' Ken- 
nel Association, the Fox-Terrier Club, etc. 

One volume, 366 pages, 5^x8^ inches. With 241 illustrations. 

Cloth, $3.25 net. 



"The reception accorded to the first edition has proved that 
a small text-book of the kind Avas distinctly wanted, and in pre- 
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illness and other causes have allowed the first to remain so long 
out of print. 

By the request of numerous friends^ the work has been en- 
larged to include symptoms and general details of treatment other 
than that which may be described as purely surgical, although the 
original idea of the author to keep the book as a handy manual for 
their final-year student has still been adhered to. 

The introduction of antiseptics has revolutionized all of the 
old-fashioned ideas, and has benefited the animal world to almost 
as great an extent as that of man. 

It is true that we have not quite the same advantages as our 
confreres in human surgical practice, but it is astonishing what 
can be done by strict attention to the principles introduced by the 
discoveries of Pasteur, and applied to surgery by the teachings of 
Lister. 

Operations which only a few years ago were looked upon 
beforehand with dread are now done every day, and owners of pet 
animals have learned to appreciate the value of modern antiseptic 
methods almost #s much as the members of the profession them- 
selves." — Extract from Preface. 

W. T. Keener & Co., Chicago. 



SPECIMEN PAGE. 



OPERATIONS ON THE MOUTH, PHARYNX, ETC. 133 

After-treatment consists merely in the application of a 
little antiseptic lotion (boric acid, chinosol, or permanganate 
of potash) several times a day. 

Sarcoma or Carcinoma — Symptoms. — As a general rule 
the first signs will merely be a capricious appetite and diffi- 
culty in swallowing, the animal appearing to have a very sore 
throat. There is salivation, and, after the trouble has existed 





-7=?e^/-/ 



Fig. 102. — Carcinoma of the 
Pharynx and Cervical Glands 
of a Terrier. 



Fig. 103. — Endothelioma per 
forating the Palate of a Great 
Dane. 



for a few weeks, a gradual emaciation of the body will be 
observed. It is not uncommon upon discovering a sore at 
the back of the mouth, such as is illustrated in Fig. 102, for a 
diagnosis to be made of an injury from a sharp bone or a 
piece of stick. This had been actually done in each of the 
cases from which Figs. 102 and 103 were sketched. All doubt 
on this question can be set aside if the wound has a ragged, 
ulcerated appearance, shows no tendency to heal after careful 



AN UNIVERSAL STANDARD. 



FRIEDBERGER & FROHNER'S 
VETERINARY PATHOLOGY. 

(Authorized Translation) 

By M. H. HAYES, F. R. C. V. S. 
Author of "Points of the Horse," "Veterinary Notes for Horse Owners," etc. 

Edited by JOHN DUNSTAN, M. R. C. V.. S. 

Professor of Surgery and Therapeutics at the Royal (Dick) Veterinary 

College, Edinburgh. 



There has long been wanting in Veterinary literature a com- 
prehensive text-book dealing with the Diseases of Animals from 
their clinical, pathological and therapeutic standpoints and which 
might have some claim to the term "modern." This gap was effi- 
ciently rilled in Germany by Friedberger and Frohner's splendid 
production, the value of which was soon correctly estimated by 
veterinary surgeons of all nations. 

The late Captain Hayes, the most prolific English veterinary 
writer of modern times and editor of many valuable works on 
veterinary and equine matters, ever quick to appreciate merit, 
bought the right to translate the work into English. Two editions 
of the first volume were published during his life, and he was 
engaged on the translation of the second volume at the time of his 
death. Dr. Dunstan was requested hy Mrs. Hayes to complete 
this volume. The work has also been translated into French and 
Russian and is the recognized text-book in American and Euro- 
pean Veterinary Colleges. 

Two volumes, 8vo. 1,285 pages. Cloth. Price per set, $8.00 net. 



CONTENTS. 



VOLUME I. 



Chapter I, Infective Diseases ; II, Miscellaneous Infective Diseases ; III, 
Chronic Constitutional Diseases ; IV, Addenda to Infective Diseases ; 
V, Notes on Bacteriology ; VI, The Terms Infection and Contagium. 



VOLUME II. 

Chapter I, Diseases of the Organs of Digestion ; II, Diseases of the 
Esophagus; III, Diseases of the Stomach; IV, Diseases of the* Liver; 
V, Diseases of the Peritoneum; VI, Diseases of the Spleen; VII, 
Diseases of the Urinary Organs ; VIII, Diseases of the Sexual 
, Organs ; IX, Diseases of the Heart and Larger Blood Vessels ; X, 
Skin Diseases ; XI, Diseases of the Locomotory Organs ; XII, Trichi- 
nosis in Swine ; XIII, The Measles of Domestic Animals ; XIV, 
Miescher's Tubes or Rainey's Corpuscles ; XV, Diseases of the Nervous 
System ; XVI, Diseases of the Spinal Cord and of Its Membranes ; 
XVII, Diseases of the Peripheral Nerves ; XVIII, Neurosis without 
Known Anatomical Basis ; XIX, Appendix to Diseases of the Nervous 
System ; XX, Diseases of the Respiratory System ; XXI, Diseases of 
the Accessory Cavities of the Nose; XXII, Diseases of the Larynx; 
XXIII, Diseases of the Trachea and Bronchi ; XXIV, Diseases of the 
Lungs ; XXV, Diseases of the Pleura ; XXVI, Appendix to Diseases 
of the Respiratory Organs. 



OPINIONS OF FRIEDBERGER & FROHNER. 

"It is this work that I recommend to my students, and believe that of all 
works on Veterinary Medicine, it is the best ada.pted to class room use." — 
Leonard Pearson. Dean and Professor of Practice Veterinary Medicine, De- 
partment of Veterinary Medicine, University of Pennsylvania. 

"Hope you will be amply repaid for its production — this, the most modern 
and best text-book we have." — J. L. Robertson, Professor of Veterinary Medi- 
cine, New York Veterinary College. 

"I take pleasure in making - a very favorable report, after a careful review. 
on Veterinary Pathology bv Friedbere-er and Frohner, translated by M. H. 
Hayes. F. R. C. V. S.. and consider it the best work to-dav on theory and 
nractice of Veterinary Medicine for students' usp. and have recommended it to 
the students of the Chicago VeteHnarv College." 

(Signed) A. H. B A.KER. V. S., 

Dean of Faculty and Professor of Theory and Practice. 

"I find that the print is excellent, that the translator Iims put the technical 
statements' into free and easilv understood English language, making the text 
easily comprehended by the average student. You will note by the catalogue 
mailed you' this day this work has been adopted as the text-book of this 
college." — S. Stewart. M. D., D. V. S., Professor of Veterinary Medicine, Kansas 
City Veterinary College. 

"For many years Friedberger and Frohner's 'Lehrbuch der Specicllen 
Pa.thologie und Therapie der Hausthiere' has been considered by competent 
judges to be the best treatise on diseases of animals and their treatment. It 
is not alone of inestimable value to the practitioner, but it must be regarded as 
an important addition to medical literature, to which the research scholar 
gladly turns.. The work has already been translated Into French and Russian, 
and is used as a text-book in those countries. An English translation should, 
therefore, be hailed with delight, as there is no really good English work 
covering the Practice of Veterinary Medicine.' 1 -Boston Medical and Surgical 
Journal. 

In Ordering FRIEDBERGER and FROHNER to ensure latest edition speclty Hayes' Translation. 



W. T. Keener & Co., Chicago. 



The only strictly up-to-date Veterinary Physiology in the English language. 

ESSENTIALS OF PHYSIOLOGY FOR 
VETERINARY STUDENTS- 

By D. NOEL PATON, M. D., B. Sc, F. R. C. P., Ed. 

Superintendent of Research Laboratory of the Royal College of Physicians 
of Edinburgh; Lecturer on Physiology, School of Medicine of the 
Royal College, Edinburgh; Examiner in Physiology in the University 
of Glasgow and for the Royal College of Physicians, Edinburgh, and 
late Examiner in the University of Edinburgh; Examiner in Physiology 
for the Royal College of Veterinary Surgeons ; Late Professor of 
Physiology, Royal Dick Veterinary College, Edinburgh. 

One volume, 428 pages, 5^4x8^ inches. Profusely illustrated. 

Cloth, $3.00 net. 

Between the Physiology of man and that of domestic animals 
there is no fundamental difference and most of our knowledge of 
human physiology has been acquired from experiments upon the 
lower animals. But while the tissues of a man, a dog and a horse 
act much in the same manner, the mode of nutrition of these tis- 
sues is somewhat different and requires special attention in the 
case of each. 

In this volume the attempt is made to give the Essentials of 
General Physiology and of the special physiology of the domestic 
animals in a form suitable to the requirements of students and 
practitioners of veterinary medicine. 

OPINION. 

"The examination which we have been able to give this work 
has left a very favorable impression, as it appears that the essen- 
tials have been included, with nothing omitted except the padding, 
which in some text-books of physiology require a vast amount of 
reading to extract them, resulting in much confusion to students 
and those who do not have the time nor inclination to make the 
search for facts. 

"We recommend the work heartily in the sense that it reduces 
the study of physiology to a 'reasonable' basis, and the author has 
done for the reader what is a difficult task upon his own account. 
Well printed, well bound, intelligently illustrated, Messrs. Keener 
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reasonable price." — Am. Vet. Review. 

W. T. Keener & Co., Chicago. 



Specimen Page of Paton's Veterinary Physiology. 



THE FOOD AND DIGESTION 



307 



up and prepared for digestion. In the horse the lips are 

long and prehensile, and are essential for the taking of food. 

Into the mouth three pairs of compound glands — the 

SaliYary Glands — open. The 

parotid, lined entirely by 

enzyme-secreting epithelium, 

opens on the side of the 

cheek, while the submaxillary 

gland, composed partly of acini 

with enzyme - secreting, and 

partly of acini with mucin- 

secreting epithelium, and the 

sub-lingual, composed entirely 

of mucin-secreting acini, open 

under the tongue (S.C.). 

The tongue in the horse is 
smooth, but in the ox, and 
especially in the cat, it is 
covered with a fine fur of 
processes, the filiform papilla, 
which are of use in passing 
the food backwards along its 
surface in the act of swallow- 
ing. (For Organs of Taste see 
p. 132.) 

Posteriorly, the mouth opens 
into the pharynx (Ph.) or upper 
part of the gullet. In the 
horse the soft palate is very 
long, reaching to the base 
of the epiglottis, and, unless 
during swallowing, shutting off 
the mouth from the pharynx 
(Fig. 137). On each side, 
between the mouth and the 

pharynx, is the tonsil (T.), an almond-like mass of lymphoid 
tissue. The pharynx is a cavity which can be shut off 
above from the posterior nares by raising the soft palate, 
and by pulling forward the posterior pharyngeal wall. It is 
surrounded by three constrictor muscles, which, by contracting 




FlG. 138. — Diagram of the Parts of 
the Alimentary Canal, from Mouth 
to. Anus. T., Tonsils; Ph., 
Pharynx; S.C., Salivary Glands; 
Oc, OEsophagus ; C, Cardiac; 
Py., Pyloric Portion of Stomach ; 
D. , Duodenum; Li., Liver; P., 
Pancreas; J"., Jejunum; /..Ileum; 
V., Vermiform Appendix; Col., 
Colon ; R., Rectum. 



ANNOUNCEMENT 



PATHOLOGY 



OF 



METABOLISM 



Edited by 

CARL VON NOORDEN 

FIRST MEDICAL CLINIC, VIENNA. LATE OF FRANKFORT. 



Contributions by 

ADALBERT CZERNY (Breslaui, CARL DAPPER (Kissingen), 
FR. KRAUS (Berlin i, OTTO LOWEI (Vienna), ADOLF 
MAGNUS-LEVY (Berlin), M. MATTHES (Cologne), LEO 
MORH (Berlin), CARL NEUBERG (Berlin), HUGO SALOMON 
(Frankfort\ AD. SCHMIDT (Dresden), FRANZ STEINITZ 
(Breslaui, H. STRAUSS (Berlin), W. WEINTRAUD I Wiesbaden). 



SECOND EDITION 
Authorized English Translation. Edited with Additions. 

By 

I. WALKER HALL, M. D. 

Professor of Pathology, University College, Bristol. 



THREE VOLUMES, 8vo. - - CLOTH, $16.00 

Payable, $4.00 on receipt of Volume One; $6.00 on receipt 
of Volume Two and $6.00 on receipt of Volume Three 



W. T. KEENER & CO., CHICAGO 
1906 



PREFACE TO THE_ENGLISH EDITION. 

An English Edition of von Noorden's well-known "Lehrbuch 
Stoffwechsel" does not require any specific introduction. 

Although the arrangement of the sections and their contents is 
the same as that of the first edition, the present text is mainly due 
to the co-operation of a number of workers in this branch of 
Medical Science. In his preface to the first German Edition, 
von Noorden acknowledged the encouragement and assistance of 
Gerhardt, von Jurgensen and Riegel ; in his introduction to the 
second edition, he expresses his grateful thanks to the collabora- 
tors, "whose unflagging arid zealous work alone has made it possi- 
ble to bring out, instead of a second edition of my text-book, a 
hand-book of the . pathology of metabolism" worthy of the extent 
and importance of the subject. 

The length and style of the German original has restricted the 
addition of the more recent work in detail. The additions made 
to both the text and bibliography have conformed to the general 
principle of the work in presenting a compilation of facts and a 
critical discussion of hypothesis rather than the enunciation of 
theories ; they have also been selected in harmony with the view 
of von Noorden and others, that experiments upon animals should 
be cited only in connection with acute conditions ; as it is so difficult 
to compare them with the conditions which obtain in the chronic 
diseases of human beings, these addenda have been incorporated 
in the text. 

It is a pleasure to express my thanks to my colleagues for 
their translations, to my friend Professor T. H. Milroy, for the 
many valuable suggestions and to the University College Demon- 
strator in Pathology, Dr. Carey Coombs, for his careful prepara- 
tion of the indices. 



CONTENTS OF THE VOLUMES. 

Volume I. 

The Physiology of Metabolism. 

By ADOLPH MAGNUS LEVY. 

Volume II. 

Subject. Author. Translator, 

Hunger and Chronic Inanition. . v. Noorden <\. Jex Blake, M IV 

Over Feeding v. Noorden R. W. Marsden, M. D. 



Subject. - Author. Translator. 
Fever and Infection F. Kraus J. O. Wakelin Bar- 
rett, D. Sc. M. D. 
Stomach and Intestinal Dis- 
eases Ad. Schmidt H. French, M. D., F. 

R. C. P. 

Liver Diseases W. Weintraud R. W. Webster, M. D. 

Respiratory and Circulatory- 
Diseases M'. Matthes A. Jex Blake, M. D. 

Blood Diseases H. Strauss J. A. Milroy, M. A., 

M. D. 
Renal Diseases v. Noorden C. Edgeworth, M. D. 



Volume III. 

Subject. Author. Translator. 

Diabetes Carl von Noorden . . H. French, M. D., 

F. R. C. P. 

Obesity Carl von Noorden.. D. Spence, Ph. D. 

Gout Carl von Noorden . . JR.. W. Webster, M. D. 

Diabetes Insipidus and Addi- 
son's Disease Leo Mohr T. J. Horder, M. D. 

Thyroid Gland A. Magnus Levy . . A. Jex Blake, M. D. 

Carbohydraturia Carl Neuberg J. Dixon Mann, M. D. 

F. R. C. P. 

Cystinuria 

Alcaptonuria, Oxaluria, Phos- 

phaturia Carl Neuberg W. H. Hurtley, D. 

Sc. 

Nervous System 

Muscles Leo M'ohr A. Edwards 

Bones 

Cancerous Affections Adolf Schmidt .... W. Cramer, Ph. D. 

Skin Diseases Salomen and 

von Noorden J. A. Nixon, M. B. 

Childhood Czerny and 

Steinitz J. Fortescue Brick- 
dale, M. D. 

Influence of Drugs and Poisons. Otto Lowei J. Fortescue Brick- 
dale, M. D. 

Bath and Climate Matthes J. A. Nixon, M. B. 

Phototherapeutics H. Salomen A. Edwards. 



Volume I will be published in the late autumn of 1906. Volumes II 
and III in 1907. 



OCT 21 1906 



